Compendium of Cancer Genome Aberrations

Myelodysplastic neoplasm with increased blasts

Revision as of 14:04, 3 November 2023 by Bailey.Glen (talk | contribs) (Created page with "{{DISPLAYTITLE:Myelodysplastic neoplasm with increased blasts}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote class='block...")
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)

Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-11-03. The original page can be found at HAEM4:Myelodysplastic Syndrome (MDS) with Excess Blasts.

Primary Author(s)*

Put your text here (Name and affiliation; example: Jane Smith, PhD, Institute of Genomics)

Cancer Category/Type

Myelodysplastic Syndrome

Cancer Sub-Classification / Subtype

Myelodysplastic Syndrome with excess blasts (MDS-EB)

Definition / Description of Disease

Myelodysplastic syndrome (MDS) with excess blasts (EB) is a category of MDS characterized by <20% blasts in both peripheral blood and bone marrow. MDS-EB type 1 (MDS-EB-1) is classified as <5% blasts in the blood and <10% blasts in the bone marrow. MDS-EB type 2 (MDS-EB-2) is classified as 5-19% blasts in the blood and 10-19% blasts in the bone marrow with the presence of Auer rods[1][2]. The category of erythroid/myeloid-type acute erythroid leukemia in the 2008 WHO classification is now categorized as MDS-EB[3]. In addition, the majority of myelodysplastic syndrome with marrow fibrosis (MDS-F) belongs to myelodysplastic syndrome with excess blasts and fibrosis (MDS-EB-F)[4][5][6].

Synonyms / Terminology

Refractory anemia with excess blasts, erythroid/myeloid-type acute erythroid leukemia

Epidemiology / Prevalence

MDS-EB accounts for 40% of all cases of MDS (Arber DA, et al., (2016).)

  • Occurs mainly in patients aged greater than 50 years old

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table)

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)


editv4:Clinical Features
The content below was from the old template. Please incorporate above.

The clinical features are often nonspecific and are generally related to the corresponding cytopenias such as anemia, thrombocytopenia and neutropenia. The recommended thresholds for cytopenia suggested by International Prognostic Scoring System (IPSS) (PMID: 22740453) include:

  • Hemoglobin concentration: <10 g/dL
  • Absolute neutrophil count: <1.8 x109/L AND
  • Platelet count: <100 x109/L

Sites of Involvement

Peripheral blood and bone marrow

Morphologic Features

The morphologic features of the peripheral blood and bone marrow are currently the gold standard for the diagnosis of MDS[3].

Categories Morphologic Features
Blood Abnormalities in all three myeloid cell lines; blasts commonly present
Bone marrow
  • Often hypercellular
  • Blasts aggregated
 Erythropoiesis: erythropoiesis increased, dyserythropoiesis: abnormally lobated nuclei, internuclear bridging
Granulopoiesis: dysplasia, nuclear hyposegmentation or hypersegmented nuclei or cytoplasmic hypogranularity
Dysmegakaryopoiesis: micromegakaryocytes often seen; multiple widely separated nuclei also can occur

Immunophenotype

Put your text here and/or fill in the table

Finding Marker
Positive (universal) CD34 and/or KIT (CD117), CD38, HLA-DR and CD13 and/or CD33
Positive (subset) CD7 (20%), CD56 (10%)

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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).


editv4:Chromosomal Rearrangements (Gene Fusions)
The content below was from the old template. Please incorporate above.

None


editv4: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: 2-19% blasts in peripheral blood or 5-19% myeloblasts in bone marrow
  • Prognosis: Patients with MDS-EB-1 have a median survival of 16 months with 25% cases progressing to AML. While patients with MDS-EB-2 have a median survival of 9 months with 33% cases progressing to AML[7][8][9]. TP53, RUNX1 or ASXL1 mutations are associated with poor prognosis in MDS-EB with erythroid predominance[10][11].
  • Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the therapy of choice for MDS-EB in childhood with the best available donor[12]. Azacitidine, a DNA methyltransferase-inhibitor, has been reported to increase the overall survival for adult patients with high-risk MDS (MDS-REB) in comparison with conventional care[13].

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table (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.)

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).

editv4:Genomic Gain/Loss/LOH
The content below was from the old template. Please incorporate above.
  • Nonspecific cytogenetic abnormalities have been observed in 30-50% of MDS-EB cases.
  • Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype[14].

Characteristic Chromosomal Patterns

Put your text here (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)

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).

editv4:Characteristic Chromosomal Aberrations / Patterns
The content below was from the old template. Please incorporate above.

Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (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.)

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).


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.


editv4:Gene Mutations (SNV/INDEL)
The content below was from the old template. Please incorporate above.

Most frequent mutations: SRSF2, IDH1, IDH2, ASXL1, CBL, RUNX1, RAS

Other Mutations

None

Epigenomic Alterations

No

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

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
editv4:Genes and Main Pathways Involved
The content below was from the old template. Please incorporate above.
  • SRSF2: involved in pre-mRNA splicing
  • IDH1/IDH2: involved in hypoxia pathways
  • ASXL1: involved in chromatin remodeling
  • CBL: involved in targeting substrates for degradation by the proteasome
  • RUNX1: transcription factor for hematopoiesis cells
  • RAS: involved in RAS/MAPK pathway

Genetic Diagnostic Testing Methods

  • Quantification of dysplasia: Microscopy
  • Pathology: Immunophenotyping by flow cytometry
  • Genetics: Conventional karyotyping. Fluorescence in situ hybridization (FISH) analysis, microarray and sequencing

Familial Forms

No

Additional Information

No

Links

Put your links here (use link icon at top of page)

References

(use the "Cite" icon at the top of the page) (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. 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.)

  1. ↑ Greenberg, P.; et al. (1997-03-15). "International scoring system for evaluating prognosis in myelodysplastic syndromes". Blood. 89 (6): 2079–2088. ISSN 0006-4971. PMID 9058730.
  2. ↑ Germing, Ulrich; et al. (2006-01). "Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals". British Journal of Haematology. 132 (2): 162–167. doi:10.1111/j.1365-2141.2005.05853.x. ISSN 0007-1048. PMID 16398650. Check date values in: |date= (help)
  3. ↑ 3.0 3.1 Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.
  4. ↑ Lambertenghi-Deliliers, G.; et al. (1991-06). "Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity". British Journal of Haematology. 78 (2): 161–166. doi:10.1111/j.1365-2141.1991.tb04411.x. ISSN 0007-1048. PMID 1712222. Check date values in: |date= (help)
  5. ↑ Bae, E.; et al. (2013-12). "Differential diagnosis of myelofibrosis based on WHO 2008 criteria: acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis". International Journal of Laboratory Hematology. 35 (6): 629–636. doi:10.1111/ijlh.12101. ISSN 1751-553X. PMID 23693053. Check date values in: |date= (help)
  6. ↑ Orazi, Attilio (2007). "Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases". Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology. 74 (2): 97–114. doi:10.1159/000101709. ISSN 1015-2008. PMID 17587881.
  7. ↑ Germing, Ulrich; et al. (2006-12). "Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes". Haematologica. 91 (12): 1596–1604. ISSN 1592-8721. PMID 17145595. Check date values in: |date= (help)
  8. ↑ Strupp, Corinna; et al. (2003-05). "Refractory anemia with excess of blasts in transformation: analysis of reclassification according to the WHO proposals". Leukemia Research. 27 (5): 397–404. doi:10.1016/s0145-2126(02)00220-5. ISSN 0145-2126. PMID 12620291. Check date values in: |date= (help)
  9. ↑ Amin, H. M.; et al. (2005-09). "Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias". Leukemia. 19 (9): 1567–1572. doi:10.1038/sj.leu.2403876. ISSN 0887-6924. PMID 16049515. Check date values in: |date= (help)
  10. ↑ Grossmann, V.; et al. (2013-09). "Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics". Leukemia. 27 (9): 1940–1943. doi:10.1038/leu.2013.144. ISSN 1476-5551. PMID 23648669. Check date values in: |date= (help)
  11. ↑ Hasserjian, Robert P.; et al. (2010-03-11). "Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification". Blood. 115 (10): 1985–1992. doi:10.1182/blood-2009-09-243964. ISSN 1528-0020. PMC 2942006. PMID 20040759.
  12. ↑ Hasle, Henrik (2016-12-02). "Myelodysplastic and myeloproliferative disorders of childhood". Hematology. American Society of Hematology. Education Program. 2016 (1): 598–604. doi:10.1182/asheducation-2016.1.598. ISSN 1520-4383. PMC 6142519. PMID 27913534.
  13. ↑ Gore, Steven D.; et al. (2013-07). "A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial". Haematologica. 98 (7): 1067–1072. doi:10.3324/haematol.2012.074831. ISSN 1592-8721. PMC 3696610. PMID 23585522. Check date values in: |date= (help)
  14. ↑ Germing, Ulrich; et al. (2006-12). "Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes". Haematologica. 91 (12): 1596–1604. ISSN 1592-8721. PMID 17145595. Check date values in: |date= (help)

Notes

*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.

*Citation of this Page: “Myelodysplastic neoplasm with increased blasts”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/3/2023, https://ccga.io/index.php/HAEM5:Myelodysplastic_neoplasm_with_increased_blasts.

Other Sections

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.

Retrieved from "https://ccga.io/index.php?title=HAEM5:Myelodysplastic_neoplasm_with_increased_blasts&oldid=12768"