View source for HAEM5:Childhood myelodysplastic neoplasm with increased blasts

{{DISPLAYTITLE:Childhood myelodysplastic neoplasm with increased blasts}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

{{Under Construction}}

<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Refractory Cytopenia of Childhood]].
}}</blockquote>

<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

==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__

==WHO Classification of Disease==

{| class="wikitable"
!Structure
!Disease
|-
|Book
|Haematolymphoid Tumours (5th ed.)
|-
|Category
|Myeloid proliferations and neoplasms
|-
|Family
|Myelodysplastic neoplasms
|-
|Type
|Myelodysplastic neoplasms of childhood
|-
|Subtype(s)
|Childhood myelodysplastic neoplasm with increased blasts
|}

==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. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)

<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)

<span class="blue-text">EXAMPLE:</span> Fatigue

<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias

<span class="blue-text">EXAMPLE:</span> 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. Do not delete table.'') </span>

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
|-
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
|-
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
|-
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> 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
|-
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|Yes
|No
|Yes
|<span class="blue-text">EXAMPLE:</span>

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. Do not delete table.'') </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
|-
|<span class="blue-text">EXAMPLE:</span>

7
|<span class="blue-text">EXAMPLE:</span> Loss
|<span class="blue-text">EXAMPLE:</span>

chr7:1- 159,335,973 [hg38]
|<span class="blue-text">EXAMPLE:</span>

chr7
|Yes
|Yes
|No
|<span class="blue-text">EXAMPLE:</span>

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).
|-
|<span class="blue-text">EXAMPLE:</span>

8
|<span class="blue-text">EXAMPLE:</span> Gain
|<span class="blue-text">EXAMPLE:</span>

chr8:1-145,138,636 [hg38]
|<span class="blue-text">EXAMPLE:</span>

chr8
|No
|No
|No
|<span class="blue-text">EXAMPLE:</span>

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. Do not delete table.'')</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
|-
|<span class="blue-text">EXAMPLE:</span>

Co-deletion of 1p and 18q
|Yes
|No
|No
|<span class="blue-text">EXAMPLE:</span>

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 as 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. Do not delete table.'') </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
|-
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations

<span class="blue-text">EXAMPLE:</span>

EGFR; Exon 20 mutations

<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|<span class="blue-text">EXAMPLE:</span> TSG
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)

<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
|
|
|
|<span class="blue-text">EXAMPLE:</span>  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. Do not delete table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|-
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|<span class="blue-text">EXAMPLE:</span>  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: Highlight text to which you want to add a link in this section or elsewhere, 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 by 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 />

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==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]]