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HAEM5:Childhood myelodysplastic neoplasm with increased blasts (view source)
Revision as of 14:04, 3 November 2023
, 14:04, 3 November 2023Created page with "{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with increased blasts}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote cl..."
{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with increased blasts}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
{{Under Construction}}
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Refractory Cytopenia of Childhood]].
}}</blockquote>
==Primary Author(s)*==
Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
__TOC__
==Cancer Category/Type==
Myelodysplastic Syndrome
==Cancer Sub-Classification / Subtype==
Refractory Cytopenia of Childhood
==Definition / Description of Disease==
Refractory Cytopenia of Childhood (RCC) is a low-grade MDS most common in childhood, which is characterized by <2% blood blasts and <5% bone marrow blasts and persistent cytopenia<ref>{{Cite journal|last=Hasle|first=H.|last2=Niemeyer|first2=C. M.|last3=Chessells|first3=J. M.|last4=Baumann|first4=I.|last5=Bennett|first5=J. M.|last6=Kerndrup|first6=G.|last7=Head|first7=D. R.|date=2003-02|title=A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases|url=https://pubmed.ncbi.nlm.nih.gov/12592323|journal=Leukemia|volume=17|issue=2|pages=277–282|doi=10.1038/sj.leu.2402765|issn=0887-6924|pmid=12592323}}</ref>. Since more than 80% RCC has a hypocellular bone marrow, it is important to distinguish RCC with aplastic anemia from other bone marrow failure disorders<ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref>. Aplastic anemia is an autoimmune-mediated disorder, while RCC is caused by a clonal stem cell defect with the potential to progress to an advanced disease. The presence of micromegakaryocytes is a strong indicator of RCC. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment<ref name=":0">Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.</ref>.
==Synonyms / Terminology==
Refractory Cytopenia of Childhood (RCC)
==Epidemiology / Prevalence==
RCC accounts for 50% of all cases of MDS<ref name=":0" /> <ref>{{Cite journal|last=Passmore|first=S. Jane|last2=Chessells|first2=Judith M.|last3=Kempski|first3=Helena|last4=Hann|first4=Ian M.|last5=Brownbill|first5=Pat A.|last6=Stiller|first6=Charles A.|date=2003-06|title=Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival|url=https://pubmed.ncbi.nlm.nih.gov/12780790|journal=British Journal of Haematology|volume=121|issue=5|pages=758–767|doi=10.1046/j.1365-2141.2003.04361.x|issn=0007-1048|pmid=12780790}}</ref><ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Giagounidis|first3=Aristoteles|last4=Haas|first4=Rainer|last5=Gattermann|first5=Norbert|last6=Starke|first6=Carsten|last7=Aul|first7=Carlo|date=2012-06|title=Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/22421409|journal=Leukemia Research|volume=36|issue=6|pages=727–734|doi=10.1016/j.leukres.2012.02.014|issn=1873-5835|pmid=22421409}}</ref>.
*Most common childhood MDS
*No significant sex predilection
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
EXAMPLE Fatigue
EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
The clinical symptoms are usually related to cytopenia such as anemia, bleeding tendency, and infection. However, approximately 20% of patients have no clinical symptoms or signs<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref>.
*Hemoglobin concentration: <10 g/dL AND
*Platelet count: <150 x10<sup>9</sup>/L
</blockquote>
==Sites of Involvement==
Peripheral blood and bone marrow
==Morphologic Features==
The main morphologic features of the peripheral blood smear and bone marrow are for the diagnosis of RCC<ref name=":0" />.
{| class="wikitable"
|+
!'''Categories'''
!'''Morphologic Features'''
|-
|Peripheral blood
|Anisopoikilocytosis and macrocytosis; neutropenia with pseudo-Pelger-Huet nulei, hypogranularity or agranularity,
|-
|Bone marrow aspirate/biopsy
|Erythropoiesis: immature erythroid precursors, nuclear budding, multinuclearity, internuclear bridging;
Graulopoiesis: pseudo-Pelger-Huet nulei, hypogranularity or agranularity, macrocytic bands;
Megakaryopoiesis: absent or very few, however, micromegakaryocyte is crucial for the diagnosis.
|}
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
CD61, CD41, von Willebrand factor are useful to help detect the micromegakaryocyte. No increase of CD34 staining should be observed, which indicates the progression of high grade MDS<ref name=":0" />.
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
No
</blockquote>
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
*Diagnosis: <2% blood blasts and <5% bone marrow blasts and persistent cytopenia
*Prognosis: In RCC, patients with monosomy 7 have a higher probability of progression<ref>{{Cite journal|last=Passmore|first=S. Jane|last2=Chessells|first2=Judith M.|last3=Kempski|first3=Helena|last4=Hann|first4=Ian M.|last5=Brownbill|first5=Pat A.|last6=Stiller|first6=Charles A.|date=2003-06|title=Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival|url=https://pubmed.ncbi.nlm.nih.gov/12780790|journal=British Journal of Haematology|volume=121|issue=5|pages=758–767|doi=10.1046/j.1365-2141.2003.04361.x|issn=0007-1048|pmid=12780790}}</ref><ref>{{Cite journal|last=Pui|first=Ching-Hon|last2=Schrappe|first2=Martin|last3=Ribeiro|first3=Raul C.|last4=Niemeyer|first4=Charlotte M.|date=2004|title=Childhood and adolescent lymphoid and myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/15561680|journal=Hematology. American Society of Hematology. Education Program|pages=118–145|doi=10.1182/asheducation-2004.1.118|issn=1520-4391|pmid=15561680}}</ref><ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref>. Patients with trisomy 8 or a normal karyotype are unlikely to progress to advanced MDS.
*Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for RCC patients. This treatment is suitable for patients with monosomy 7 or a complex karyotype in the early stage of the process. Some of the RCC patients benefit from immunosuppressive therapy, although it is unclear whether the immunosuppressive therapy has the risk of relapse long-term<ref>{{Cite journal|last=Hasegawa|first=Daisuke|last2=Manabe|first2=Atsushi|last3=Yagasaki|first3=Hiroshi|last4=Ohtsuka|first4=Yoshitoshi|last5=Inoue|first5=Masami|last6=Kikuchi|first6=Akira|last7=Ohara|first7=Akira|last8=Tsuchida|first8=Masahiro|last9=Kojima|first9=Seiji|date=2009-12|title=Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99)|url=https://pubmed.ncbi.nlm.nih.gov/19499580|journal=Pediatric Blood & Cancer|volume=53|issue=6|pages=1011–1015|doi=10.1002/pbc.22121|issn=1545-5017|pmid=19499580}}</ref><ref>{{Cite journal|last=Yoshimi|first=Ayami|last2=van den Heuvel-Eibrink|first2=Marry M.|last3=Baumann|first3=Irith|last4=Schwarz|first4=Stephan|last5=Simonitsch-Klupp|first5=Ingrid|last6=de Paepe|first6=Pascale|last7=Campr|first7=Vit|last8=Kerndrup|first8=Gitte Birk|last9=O'Sullivan|first9=Maureen|date=2014-04|title=Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood|url=https://pubmed.ncbi.nlm.nih.gov/24162791|journal=Haematologica|volume=99|issue=4|pages=656–663|doi=10.3324/haematol.2013.095786|issn=1592-8721|pmc=3971075|pmid=24162791}}</ref>.
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
7
|EXAMPLE Loss
|EXAMPLE
chr7:1- 159,335,973 [hg38]
|EXAMPLE
chr7
|Yes
|Yes
|No
|EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|EXAMPLE
8
|EXAMPLE Gain
|EXAMPLE
chr8:1-145,138,636 [hg38]
|EXAMPLE
chr8
|No
|No
|No
|EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
Monosomy 7 is the most frequent cytogenetic abnormality of RCC patients, followed by trisomy 8 and other abnormalities, including complex karyotypes<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref><ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref><ref>{{Cite journal|last=Gupta|first=Ruchi|last2=Harankhedkar|first2=Shivangi|last3=Rahman|first3=Khaliqur|last4=Singh|first4=Manish K.|last5=Chandra|first5=Dinesh|last6=Mittal|first6=Navkirti|last7=Gupta|first7=Anshul|last8=Nityanand|first8=Soniya|date=2018-10|title=Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review|url=https://pubmed.ncbi.nlm.nih.gov/30369728|journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion|volume=34|issue=4|pages=602–611|doi=10.1007/s12288-018-0941-1|issn=0971-4502|pmc=6186231|pmid=30369728}}</ref>.
</blockquote>
==Characteristic Chromosomal Patterns==
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
Monosomy 7 (CCHMC), trisomy 8 and other abnormalities, including complex karyotypes.
Pictures are needed to be upload!!<br />
</blockquote>
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations
EXAMPLE:
EGFR; Exon 20 mutations
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
*Mutations are less common than in adult MDS with a different profile
*Most frequent mutations: ''RAS/MAPK, SAMD9/SAMD9L, GATA2''<ref>{{Cite journal|last=Schwartz|first=Jason R.|last2=Ma|first2=Jing|last3=Lamprecht|first3=Tamara|last4=Walsh|first4=Michael|last5=Wang|first5=Shuoguo|last6=Bryant|first6=Victoria|last7=Song|first7=Guangchun|last8=Wu|first8=Gang|last9=Easton|first9=John|date=2017-11-16|title=The genomic landscape of pediatric myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/29146900|journal=Nature Communications|volume=8|issue=1|pages=1557|doi=10.1038/s41467-017-01590-5|issn=2041-1723|pmc=5691144|pmid=29146900}}</ref><ref>{{Cite journal|last=Wlodarski|first=Marcin W.|last2=Hirabayashi|first2=Shinsuke|last3=Pastor|first3=Victor|last4=Starý|first4=Jan|last5=Hasle|first5=Henrik|last6=Masetti|first6=Riccardo|last7=Dworzak|first7=Michael|last8=Schmugge|first8=Markus|last9=van den Heuvel-Eibrink|first9=Marry|date=2016-03-17|title=Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents|url=https://pubmed.ncbi.nlm.nih.gov/26702063|journal=Blood|volume=127|issue=11|pages=1387–1397; quiz 1518|doi=10.1182/blood-2015-09-669937|issn=1528-0020|pmid=26702063}}</ref>.
===Other Mutations===
No
</blockquote>
==Epigenomic Alterations==
No
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|EXAMPLE: Unregulated cell division
|-
|EXAMPLE: KMT2C and ARID1A; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
*''RAS/MAPK'': involved in ''MAPK'' tyrosine Kinase pathway
*''SAMD9/SAMD9L'': involved in regulating the growth and proliferation and differentiation of cells
*''GATA2'': involved in regulating transcription of genes related with the development and proliferation of hematopoietic and endocrine cell lineages
</blockquote>
==Genetic Diagnostic Testing Methods==
Bone marrow minimal histological criteria for refractory cytopenia of childhood<ref>Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.</ref><ref>{{Cite journal|last=Iwafuchi|first=Hideto|date=2018|title=The histopathology of bone marrow failure in children|url=https://pubmed.ncbi.nlm.nih.gov/29998978|journal=Journal of clinical and experimental hematopathology: JCEH|volume=58|issue=2|pages=68–86|doi=10.3960/jslrt.18018|issn=1880-9952|pmc=6413145|pmid=29998978}}</ref>. Refractory cytopenia of childhood is defined as persistent cytopenia with <5% blasts in bone marrow and <2% blasts in peripheral blood. The criteria of dysplasia must be fulfilled in ≥2 cell lineages or ≥10% of cells within one cell lineage on bone marrow aspirate smears. See table:
{| class="wikitable"
|+
!Cellularity
!Erythropoiesis
!Granulopoiesis
!Megakaryopoiesis
|-
|Variable
|A few clusters of ≥20 erythroid precursors.
Arrest in maturation, with increased number of proerythroblasts.
Increased number of mitoses.
|No minimal diagnostic criteria.
|Unequivocal micromegakaryocytes;
immunohistochemistry is obligatory (CD61, CD41, CD42b);
other dysplastic changes in variable numbers.
|}
In addition, RCC must be differentiated from aplastic anemia, bone marrow failure syndromes, infection, nutritional deficiencies, and metabolic diseases.
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
==Additional Information==
Put your text here
==Links==
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
'''
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>''Citation of this Page'': “Childhood myelodysplastic neoplasm with increased blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Childhood_myelodysplastic_neoplasm_with_increased_blasts</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
{{Under Construction}}
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Refractory Cytopenia of Childhood]].
}}</blockquote>
==Primary Author(s)*==
Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
__TOC__
==Cancer Category/Type==
Myelodysplastic Syndrome
==Cancer Sub-Classification / Subtype==
Refractory Cytopenia of Childhood
==Definition / Description of Disease==
Refractory Cytopenia of Childhood (RCC) is a low-grade MDS most common in childhood, which is characterized by <2% blood blasts and <5% bone marrow blasts and persistent cytopenia<ref>{{Cite journal|last=Hasle|first=H.|last2=Niemeyer|first2=C. M.|last3=Chessells|first3=J. M.|last4=Baumann|first4=I.|last5=Bennett|first5=J. M.|last6=Kerndrup|first6=G.|last7=Head|first7=D. R.|date=2003-02|title=A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases|url=https://pubmed.ncbi.nlm.nih.gov/12592323|journal=Leukemia|volume=17|issue=2|pages=277–282|doi=10.1038/sj.leu.2402765|issn=0887-6924|pmid=12592323}}</ref>. Since more than 80% RCC has a hypocellular bone marrow, it is important to distinguish RCC with aplastic anemia from other bone marrow failure disorders<ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref>. Aplastic anemia is an autoimmune-mediated disorder, while RCC is caused by a clonal stem cell defect with the potential to progress to an advanced disease. The presence of micromegakaryocytes is a strong indicator of RCC. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment<ref name=":0">Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.</ref>.
==Synonyms / Terminology==
Refractory Cytopenia of Childhood (RCC)
==Epidemiology / Prevalence==
RCC accounts for 50% of all cases of MDS<ref name=":0" /> <ref>{{Cite journal|last=Passmore|first=S. Jane|last2=Chessells|first2=Judith M.|last3=Kempski|first3=Helena|last4=Hann|first4=Ian M.|last5=Brownbill|first5=Pat A.|last6=Stiller|first6=Charles A.|date=2003-06|title=Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival|url=https://pubmed.ncbi.nlm.nih.gov/12780790|journal=British Journal of Haematology|volume=121|issue=5|pages=758–767|doi=10.1046/j.1365-2141.2003.04361.x|issn=0007-1048|pmid=12780790}}</ref><ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Giagounidis|first3=Aristoteles|last4=Haas|first4=Rainer|last5=Gattermann|first5=Norbert|last6=Starke|first6=Carsten|last7=Aul|first7=Carlo|date=2012-06|title=Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/22421409|journal=Leukemia Research|volume=36|issue=6|pages=727–734|doi=10.1016/j.leukres.2012.02.014|issn=1873-5835|pmid=22421409}}</ref>.
*Most common childhood MDS
*No significant sex predilection
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
EXAMPLE Fatigue
EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
The clinical symptoms are usually related to cytopenia such as anemia, bleeding tendency, and infection. However, approximately 20% of patients have no clinical symptoms or signs<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref>.
*Hemoglobin concentration: <10 g/dL AND
*Platelet count: <150 x10<sup>9</sup>/L
</blockquote>
==Sites of Involvement==
Peripheral blood and bone marrow
==Morphologic Features==
The main morphologic features of the peripheral blood smear and bone marrow are for the diagnosis of RCC<ref name=":0" />.
{| class="wikitable"
|+
!'''Categories'''
!'''Morphologic Features'''
|-
|Peripheral blood
|Anisopoikilocytosis and macrocytosis; neutropenia with pseudo-Pelger-Huet nulei, hypogranularity or agranularity,
|-
|Bone marrow aspirate/biopsy
|Erythropoiesis: immature erythroid precursors, nuclear budding, multinuclearity, internuclear bridging;
Graulopoiesis: pseudo-Pelger-Huet nulei, hypogranularity or agranularity, macrocytic bands;
Megakaryopoiesis: absent or very few, however, micromegakaryocyte is crucial for the diagnosis.
|}
==Immunophenotype==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Immunophenotype|The content below was from the old template. Please incorporate above.}}
CD61, CD41, von Willebrand factor are useful to help detect the micromegakaryocyte. No increase of CD34 staining should be observed, which indicates the progression of high grade MDS<ref name=":0" />.
</blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
No
</blockquote>
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
*Diagnosis: <2% blood blasts and <5% bone marrow blasts and persistent cytopenia
*Prognosis: In RCC, patients with monosomy 7 have a higher probability of progression<ref>{{Cite journal|last=Passmore|first=S. Jane|last2=Chessells|first2=Judith M.|last3=Kempski|first3=Helena|last4=Hann|first4=Ian M.|last5=Brownbill|first5=Pat A.|last6=Stiller|first6=Charles A.|date=2003-06|title=Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia in the UK: a population-based study of incidence and survival|url=https://pubmed.ncbi.nlm.nih.gov/12780790|journal=British Journal of Haematology|volume=121|issue=5|pages=758–767|doi=10.1046/j.1365-2141.2003.04361.x|issn=0007-1048|pmid=12780790}}</ref><ref>{{Cite journal|last=Pui|first=Ching-Hon|last2=Schrappe|first2=Martin|last3=Ribeiro|first3=Raul C.|last4=Niemeyer|first4=Charlotte M.|date=2004|title=Childhood and adolescent lymphoid and myeloid leukemia|url=https://pubmed.ncbi.nlm.nih.gov/15561680|journal=Hematology. American Society of Hematology. Education Program|pages=118–145|doi=10.1182/asheducation-2004.1.118|issn=1520-4391|pmid=15561680}}</ref><ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref>. Patients with trisomy 8 or a normal karyotype are unlikely to progress to advanced MDS.
*Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for RCC patients. This treatment is suitable for patients with monosomy 7 or a complex karyotype in the early stage of the process. Some of the RCC patients benefit from immunosuppressive therapy, although it is unclear whether the immunosuppressive therapy has the risk of relapse long-term<ref>{{Cite journal|last=Hasegawa|first=Daisuke|last2=Manabe|first2=Atsushi|last3=Yagasaki|first3=Hiroshi|last4=Ohtsuka|first4=Yoshitoshi|last5=Inoue|first5=Masami|last6=Kikuchi|first6=Akira|last7=Ohara|first7=Akira|last8=Tsuchida|first8=Masahiro|last9=Kojima|first9=Seiji|date=2009-12|title=Treatment of children with refractory anemia: the Japanese Childhood MDS Study Group trial (MDS99)|url=https://pubmed.ncbi.nlm.nih.gov/19499580|journal=Pediatric Blood & Cancer|volume=53|issue=6|pages=1011–1015|doi=10.1002/pbc.22121|issn=1545-5017|pmid=19499580}}</ref><ref>{{Cite journal|last=Yoshimi|first=Ayami|last2=van den Heuvel-Eibrink|first2=Marry M.|last3=Baumann|first3=Irith|last4=Schwarz|first4=Stephan|last5=Simonitsch-Klupp|first5=Ingrid|last6=de Paepe|first6=Pascale|last7=Campr|first7=Vit|last8=Kerndrup|first8=Gitte Birk|last9=O'Sullivan|first9=Maureen|date=2014-04|title=Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood|url=https://pubmed.ncbi.nlm.nih.gov/24162791|journal=Haematologica|volume=99|issue=4|pages=656–663|doi=10.3324/haematol.2013.095786|issn=1592-8721|pmc=3971075|pmid=24162791}}</ref>.
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
7
|EXAMPLE Loss
|EXAMPLE
chr7:1- 159,335,973 [hg38]
|EXAMPLE
chr7
|Yes
|Yes
|No
|EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|EXAMPLE
8
|EXAMPLE Gain
|EXAMPLE
chr8:1-145,138,636 [hg38]
|EXAMPLE
chr8
|No
|No
|No
|EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
Monosomy 7 is the most frequent cytogenetic abnormality of RCC patients, followed by trisomy 8 and other abnormalities, including complex karyotypes<ref>{{Cite journal|last=Kardos|first=Gabriela|last2=Baumann|first2=Irith|last3=Passmore|first3=S. Jane|last4=Locatelli|first4=Franco|last5=Hasle|first5=Henrik|last6=Schultz|first6=Kirk R.|last7=Starý|first7=Jan|last8=Schmitt-Graeff|first8=Annette|last9=Fischer|first9=Alexandra|date=2003-09-15|title=Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7|url=https://pubmed.ncbi.nlm.nih.gov/12763938|journal=Blood|volume=102|issue=6|pages=1997–2003|doi=10.1182/blood-2002-11-3444|issn=0006-4971|pmid=12763938}}</ref><ref>{{Cite journal|last=Niemeyer|first=Charlotte M.|last2=Baumann|first2=Irith|date=2011|title=Classification of childhood aplastic anemia and myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/22160017|journal=Hematology. American Society of Hematology. Education Program|volume=2011|pages=84–89|doi=10.1182/asheducation-2011.1.84|issn=1520-4383|pmid=22160017}}</ref><ref>{{Cite journal|last=Gupta|first=Ruchi|last2=Harankhedkar|first2=Shivangi|last3=Rahman|first3=Khaliqur|last4=Singh|first4=Manish K.|last5=Chandra|first5=Dinesh|last6=Mittal|first6=Navkirti|last7=Gupta|first7=Anshul|last8=Nityanand|first8=Soniya|date=2018-10|title=Prevalence of Chromosome 7 Abnormalities in Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Single Center Study and Brief Literature Review|url=https://pubmed.ncbi.nlm.nih.gov/30369728|journal=Indian Journal of Hematology & Blood Transfusion: An Official Journal of Indian Society of Hematology and Blood Transfusion|volume=34|issue=4|pages=602–611|doi=10.1007/s12288-018-0941-1|issn=0971-4502|pmc=6186231|pmid=30369728}}</ref>.
</blockquote>
==Characteristic Chromosomal Patterns==
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
Monosomy 7 (CCHMC), trisomy 8 and other abnormalities, including complex karyotypes.
Pictures are needed to be upload!!<br />
</blockquote>
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations
EXAMPLE:
EGFR; Exon 20 mutations
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
*Mutations are less common than in adult MDS with a different profile
*Most frequent mutations: ''RAS/MAPK, SAMD9/SAMD9L, GATA2''<ref>{{Cite journal|last=Schwartz|first=Jason R.|last2=Ma|first2=Jing|last3=Lamprecht|first3=Tamara|last4=Walsh|first4=Michael|last5=Wang|first5=Shuoguo|last6=Bryant|first6=Victoria|last7=Song|first7=Guangchun|last8=Wu|first8=Gang|last9=Easton|first9=John|date=2017-11-16|title=The genomic landscape of pediatric myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/29146900|journal=Nature Communications|volume=8|issue=1|pages=1557|doi=10.1038/s41467-017-01590-5|issn=2041-1723|pmc=5691144|pmid=29146900}}</ref><ref>{{Cite journal|last=Wlodarski|first=Marcin W.|last2=Hirabayashi|first2=Shinsuke|last3=Pastor|first3=Victor|last4=Starý|first4=Jan|last5=Hasle|first5=Henrik|last6=Masetti|first6=Riccardo|last7=Dworzak|first7=Michael|last8=Schmugge|first8=Markus|last9=van den Heuvel-Eibrink|first9=Marry|date=2016-03-17|title=Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents|url=https://pubmed.ncbi.nlm.nih.gov/26702063|journal=Blood|volume=127|issue=11|pages=1387–1397; quiz 1518|doi=10.1182/blood-2015-09-669937|issn=1528-0020|pmid=26702063}}</ref>.
===Other Mutations===
No
</blockquote>
==Epigenomic Alterations==
No
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|EXAMPLE: Unregulated cell division
|-
|EXAMPLE: KMT2C and ARID1A; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
*''RAS/MAPK'': involved in ''MAPK'' tyrosine Kinase pathway
*''SAMD9/SAMD9L'': involved in regulating the growth and proliferation and differentiation of cells
*''GATA2'': involved in regulating transcription of genes related with the development and proliferation of hematopoietic and endocrine cell lineages
</blockquote>
==Genetic Diagnostic Testing Methods==
Bone marrow minimal histological criteria for refractory cytopenia of childhood<ref>Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4<sup>th</sup> edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.</ref><ref>{{Cite journal|last=Iwafuchi|first=Hideto|date=2018|title=The histopathology of bone marrow failure in children|url=https://pubmed.ncbi.nlm.nih.gov/29998978|journal=Journal of clinical and experimental hematopathology: JCEH|volume=58|issue=2|pages=68–86|doi=10.3960/jslrt.18018|issn=1880-9952|pmc=6413145|pmid=29998978}}</ref>. Refractory cytopenia of childhood is defined as persistent cytopenia with <5% blasts in bone marrow and <2% blasts in peripheral blood. The criteria of dysplasia must be fulfilled in ≥2 cell lineages or ≥10% of cells within one cell lineage on bone marrow aspirate smears. See table:
{| class="wikitable"
|+
!Cellularity
!Erythropoiesis
!Granulopoiesis
!Megakaryopoiesis
|-
|Variable
|A few clusters of ≥20 erythroid precursors.
Arrest in maturation, with increased number of proerythroblasts.
Increased number of mitoses.
|No minimal diagnostic criteria.
|Unequivocal micromegakaryocytes;
immunohistochemistry is obligatory (CD61, CD41, CD42b);
other dysplastic changes in variable numbers.
|}
In addition, RCC must be differentiated from aplastic anemia, bone marrow failure syndromes, infection, nutritional deficiencies, and metabolic diseases.
==Familial Forms==
Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>
==Additional Information==
Put your text here
==Links==
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page <span style="color:#0070C0">(''Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "<nowiki>http://www</nowiki>." portion.'')</span>
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />
'''
==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.
<nowiki>*</nowiki>''Citation of this Page'': “Childhood myelodysplastic neoplasm with increased blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Childhood_myelodysplastic_neoplasm_with_increased_blasts</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]