Difference between revisions of "HAEM5:Acute megakaryoblastic leukaemia"

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{{DISPLAYTITLE:Acute megakaryoblastic leukaemia}}
 
{{DISPLAYTITLE:Acute megakaryoblastic leukaemia}}
−
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
+
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Acute Megakaryoblastic Leukemia (AMKL)]].
+
<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:Acute Megakaryoblastic Leukemia (AMKL)]].
 
}}</blockquote>
 
}}</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). 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>
+
<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)*==
 
==Primary Author(s)*==
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==Clinical Features==
 
==Clinical Features==
  
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
+
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"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
  
−
EXAMPLE B-symptoms (weight loss, fever, night sweats)
+
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
  
−
EXAMPLE Fatigue
+
<span class="blue-text">EXAMPLE:</span> Fatigue
  
−
EXAMPLE Lymphadenopathy (uncommon)
+
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|EXAMPLE Cytopenias
+
|<span class="blue-text">EXAMPLE:</span> Cytopenias
  
−
EXAMPLE Lymphocytosis (low level)
+
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
 
|}
 
|}
  
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
 
|-
 
|-
−
|Positive (subset)||EXAMPLE CD2
+
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
 
|-
 
|-
−
|Negative (universal)||EXAMPLE CD3
+
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
 
|-
 
|-
−
|Negative (subset)||EXAMPLE CD4
+
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
 
|}
 
|}
  
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|<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)
−
EXAMPLE 30% (add reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
−
|EXAMPLE
+
|<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).
 
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).
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!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
 
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 5%
+
|<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> 5%
 
|-
 
|-
−
|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%
+
|<span class="blue-text">EXAMPLE:</span> t(8;21)(q22;q22)||<span class="blue-text">EXAMPLE:</span> 5'RUNX1 / 3'RUNXT1||<span class="blue-text">EXAMPLE:</span> der(8)||<span class="blue-text">EXAMPLE:</span> 5%
 
|}
 
|}
  
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==Individual Region Genomic Gain / Loss / LOH==
 
==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>
+
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"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
7
 
7
−
|EXAMPLE Loss
+
|<span class="blue-text">EXAMPLE:</span> Loss
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr7
 
chr7
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|Yes
 
|Yes
 
|No
 
|No
−
|EXAMPLE
+
|<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).
 
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
+
|<span class="blue-text">EXAMPLE:</span>
  
 
8
 
8
−
|EXAMPLE Gain
+
|<span class="blue-text">EXAMPLE:</span> Gain
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
chr8
 
chr8
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|No
 
|No
 
|No
 
|No
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
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!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 
|-
 
|-
−
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
+
|<span class="blue-text">EXAMPLE:</span> 8||<span class="blue-text">EXAMPLE:</span> Gain||<span class="blue-text">EXAMPLE:</span> chr8:0-1000000
 
|-
 
|-
−
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
+
|<span class="blue-text">EXAMPLE:</span> 7||<span class="blue-text">EXAMPLE:</span> Loss||<span class="blue-text">EXAMPLE:</span> chr7:0-1000000
 
|}
 
|}
  
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==Characteristic Chromosomal Patterns==
 
==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>
+
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"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|<span class="blue-text">EXAMPLE:</span>
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|No
 
|No
 
|No
 
|No
−
|EXAMPLE:
+
|<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).
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
Line 250: Line 250:
 
==Gene Mutations (SNV / INDEL)==
 
==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>
+
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"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
+
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
  
−
EXAMPLE:
+
<span class="blue-text">EXAMPLE:</span>
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
−
EXAMPLE: BRAF; Activating mutations
+
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
−
|EXAMPLE: TSG
+
|<span class="blue-text">EXAMPLE:</span> TSG
−
|EXAMPLE: 20% (COSMIC)
+
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
  
−
EXAMPLE: 30% (add Reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
−
|EXAMPLE: IDH1 R123H
+
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
−
|EXAMPLE: EGFR amplification
+
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
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!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
 
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
 
|-
 
|-
−
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
+
|<span class="blue-text">EXAMPLE:</span> TP53||<span class="blue-text">EXAMPLE:</span> R273H||<span class="blue-text">EXAMPLE:</span> Tumor Suppressor||<span class="blue-text">EXAMPLE:</span> LOF||<span class="blue-text">EXAMPLE:</span> 20%
 
|}
 
|}
 
 
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!Type!!Gene/Region/Other
 
!Type!!Gene/Region/Other
 
|-
 
|-
−
|Concomitant Mutations||EXAMPLE IDH1 R123H
+
|Concomitant Mutations||<span class="blue-text">EXAMPLE:</span> IDH1 R123H
 
|-
 
|-
−
|Secondary Mutations||EXAMPLE Trisomy 7
+
|Secondary Mutations||<span class="blue-text">EXAMPLE:</span> Trisomy 7
 
|-
 
|-
−
|Mutually Exclusive||EXAMPLE EGFR Amplification
+
|Mutually Exclusive||<span class="blue-text">EXAMPLE:</span> EGFR Amplification
 
|}
 
|}
  
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==Genes and Main Pathways Involved==
 
==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>
+
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"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
−
|EXAMPLE: MAPK signaling
+
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
−
|EXAMPLE: Increased cell growth and proliferation
+
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
−
|EXAMPLE: Cell cycle regulation
+
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
−
|EXAMPLE: Unregulated cell division
+
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
−
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
−
|EXAMPLE:  Histone modification, chromatin remodeling
+
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
−
|EXAMPLE:  Abnormal gene expression program
+
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
 
|}
 
|}
  

Revision as of 16:47, 6 September 2024

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent 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:Acute Megakaryoblastic Leukemia (AMKL).

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Fei Yang, MD, FACMG
Oregon Health & Science University, Portland, OR

Cancer Category / Type

Acute Myeloid Leukemia

Cancer Sub-Classification / Subtype

Acute Megakaryoblastic Leukemia

Definition / Description of Disease

Acute megakaryoblastic leukemia is a myeloid disease defined by ≥20% blasts in the peripheral blood or bone marrow, of which ≥50% are of megakaryocyte lineage. In the 2016 revision to the World Health Organization (WHO) classification system, acute megakaryoblastic leukemia is a distinct entity within the section of HAEM4:Acute Myeloid Leukemia (AML), Not Otherwise Specified[1][2]. This entity does not meet the criteria for inclusion in any of the other AML groups (i.e. AML with Recurrent Genetic Abnormalities, AML with Myelodysplasia-Related Changes, or Therapy-Related Myeloid Neoplasms).

AMKL in an individual with Down syndrome should be classified as a different entity, specifically HAEM5:Myeloid proliferations associated with Down syndrome[2].

AMKL associated with t(1;22)(p13.3;q13.1), or inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) should be classified as a different entity, specifically HAEM4:Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities: HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion or HAEM5:Acute myeloid leukaemia with MECOM rearrangement[2].

Synonyms / Terminology

French-American-British (FAB) classification M7[2].

Epidemiology / Prevalence

AMKL comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients[3].

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete 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.
  • Common manifestations include cytopenias (often thrombocytopenia)[2].
  • An association between acute megakaryoblastic leukemia and mediastrinal germ cell tumors has been described[4].

Sites of Involvement

Bone marrow.

Morphologic Features

  • Megakaryoblasts are usually medium-sized to large cells with basophilic cytoplasm and a high nuclear-cytoplasmic ratio.
  • Nuclei are round, slightly irregular or indented with finely reticular chromatin and 1 - 3 nucleoli.
  • Bone marrow myelofibrosis is common.

Immunophenotype

Cytochemistry

  • Megakaryoblasts are typically negative for myeloperoxidase (MPO) and stain negatively with Sudan black B.
  • Variable reactivity to periodic acid-Schiff (PAS) staining from negative to focal or strongly positive.

Immunophenotype including:

  • One or more of the platelet glycoproteins: CD41, CD61, and CD42b
  • Myeloid-associated markers may be positive: CD13, CD33
  • CD34, CD45, and HLA-DR are often negative, especially in children
Finding Marker
Positive (universal) EXAMPLE: CD1
Positive (subset) EXAMPLE: CD2
Negative (universal) EXAMPLE: CD3
Negative (subset) EXAMPLE: CD4

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.

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 5%
EXAMPLE: t(8;21)(q22;q22) EXAMPLE: 5'RUNX1 / 3'RUNXT1 EXAMPLE: der(8) EXAMPLE: 5%


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

  • The main differential diagnoses of acute megakaryoblastic leukemia include: AML with minimal differentiation, AML-MRC, acute panmeylosis with myelofibrosis, lymphoblastic leukemia, pure erythroid leukemia, blastic transformation of chronic myeloid leukemia, and the blast phase of any other myeloproliferative neoplasm[2].

Prognosis

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. Do not delete table.)

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.

None

Chromosome Number Gain/Loss/Amp/LOH Region
EXAMPLE: 8 EXAMPLE: Gain EXAMPLE: chr8:0-1000000
EXAMPLE: 7 EXAMPLE: Loss EXAMPLE: chr7:0-1000000

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. Do not delete table.)

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.
  • No unique chromosomal abnormality is associated with AMKL.
  • Isochromosome 12p is often observed in young males with mediatinal germ tumors and AMKL[6].

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 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.)

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)
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None.

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
EXAMPLE: TP53 EXAMPLE: R273H EXAMPLE: Tumor Suppressor EXAMPLE: LOF EXAMPLE: 20%

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE: IDH1 R123H
Secondary Mutations EXAMPLE: Trisomy 7
Mutually Exclusive EXAMPLE: EGFR Amplification

Epigenomic Alterations

None.

Genes and Main Pathways Involved

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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.

None.

Genetic Diagnostic Testing Methods

  • Conventional chromosome analysis
  • FISH myeloid panel

Familial Forms

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Additional Information

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Links

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References

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  1. ↑ Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. IARC Press: Lyon, France, p162-164.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Arber, Daniel A.; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254.
  3. ↑ Gruber, Tanja A.; et al. (2015). "The biology of pediatric acute megakaryoblastic leukemia". Blood. 126 (8): 943–949. doi:10.1182/blood-2015-05-567859. ISSN 1528-0020. PMC 4551356. PMID 26186939.
  4. ↑ Nichols, C. R.; et al. (1990). "Hematologic neoplasia associated with primary mediastinal germ-cell tumors". The New England Journal of Medicine. 322 (20): 1425–1429. doi:10.1056/NEJM199005173222004. ISSN 0028-4793. PMID 2158625.
  5. ↑ Oki, Yasuhiro; et al. (2006). "Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center". Blood. 107 (3): 880–884. doi:10.1182/blood-2005-06-2450. ISSN 0006-4971. PMID 16123215.
  6. ↑ Orazi, A.; et al. (1993). "Hematopoietic precursor cells within the yolk sac tumor component are the source of secondary hematopoietic malignancies in patients with mediastinal germ cell tumors". Cancer. 71 (12): 3873–3881. doi:10.1002/1097-0142(19930615)71:123.0.co;2-1. ISSN 0008-543X. PMID 8389653.

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: “Acute megakaryoblastic leukaemia”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Acute_megakaryoblastic_leukaemia.

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