Difference between revisions of "HAEM5:Acute megakaryoblastic leukaemia"

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{{DISPLAYTITLE:Acute megakaryoblastic leukaemia}}
 
{{DISPLAYTITLE:Acute megakaryoblastic leukaemia}}
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
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}}</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); to add (or move) a row or column to a table, click nearby 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>
+
<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>
  
 
==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. Do not delete table.'') </span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
+
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
  
−
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
+
EXAMPLE B-symptoms (weight loss, fever, night sweats)
  
−
<span class="blue-text">EXAMPLE:</span> Fatigue
+
EXAMPLE Fatigue
  
−
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
+
EXAMPLE Lymphadenopathy (uncommon)
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|<span class="blue-text">EXAMPLE:</span> Cytopenias
+
|EXAMPLE Cytopenias
  
−
<span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level)
+
EXAMPLE Lymphocytosis (low level)
 
|}
 
|}
  
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
  
 
*Common manifestations include cytopenias (often thrombocytopenia)<ref name=":0" />.
 
*Common manifestations include cytopenias (often thrombocytopenia)<ref name=":0" />.
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||<span class="blue-text">EXAMPLE:</span> CD1
+
|Positive (universal)||EXAMPLE CD1
 
|-
 
|-
−
|Positive (subset)||<span class="blue-text">EXAMPLE:</span> CD2
+
|Positive (subset)||EXAMPLE CD2
 
|-
 
|-
−
|Negative (universal)||<span class="blue-text">EXAMPLE:</span> CD3
+
|Negative (universal)||EXAMPLE CD3
 
|-
 
|-
−
|Negative (subset)||<span class="blue-text">EXAMPLE:</span> CD4
+
|Negative (subset)||EXAMPLE CD4
 
|}
 
|}
  
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!Notes
 
!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)
+
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
−
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
+
EXAMPLE 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
−
|<span class="blue-text">EXAMPLE:</span>
+
|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).
 
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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−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
  
 
None.
 
None.
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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
 
|-
 
|-
−
|<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(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||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%
+
|EXAMPLE t(8;21)(q22;q22)||EXAMPLE 5'RUNX1 / 3'RUNXT1||EXAMPLE der(8)||EXAMPLE 5%
 
|}
 
|}
  
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−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Please incorporate this section into the relevant tables found in:
+
<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)
 
* Chromosomal Rearrangements (Gene Fusions)
 
* Individual Region Genomic Gain/Loss/LOH
 
* Individual Region Genomic Gain/Loss/LOH
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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. Do not delete table.'') </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.'') </span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
7
 
7
−
|<span class="blue-text">EXAMPLE:</span> Loss
+
|EXAMPLE Loss
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr7
 
chr7
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|Yes
 
|Yes
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|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).
 
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>
+
|EXAMPLE
  
 
8
 
8
−
|<span class="blue-text">EXAMPLE:</span> Gain
+
|EXAMPLE Gain
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
chr8
 
chr8
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|No
 
|No
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
  
 
None
 
None
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!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> 8||<span class="blue-text">EXAMPLE:</span> Gain||<span class="blue-text">EXAMPLE:</span> chr8:0-1000000
+
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> 7||<span class="blue-text">EXAMPLE:</span> Loss||<span class="blue-text">EXAMPLE:</span> chr7:0-1000000
+
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE 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. Do not delete table.'')</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'')</span>
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|No
 
|No
 
|No
 
|No
−
|<span class="blue-text">EXAMPLE:</span>
+
|EXAMPLE:
  
 
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).
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
  
 
*No unique chromosomal abnormality is associated with AMKL.
 
*No unique chromosomal abnormality is associated with AMKL.
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==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 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>
+
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"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations
+
|EXAMPLE: TP53; Variable LOF mutations
  
−
<span class="blue-text">EXAMPLE:</span>
+
EXAMPLE:
  
 
EGFR; Exon 20 mutations
 
EGFR; Exon 20 mutations
  
−
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
+
EXAMPLE: BRAF; Activating mutations
−
|<span class="blue-text">EXAMPLE:</span> TSG
+
|EXAMPLE: TSG
−
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|EXAMPLE: 20% (COSMIC)
  
−
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
+
EXAMPLE: 30% (add Reference)
−
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
+
|EXAMPLE: IDH1 R123H
−
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
+
|EXAMPLE: EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
−
|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
+
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
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−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
  
 
None.
 
None.
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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)
 
|-
 
|-
−
|<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%
+
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
 
|}
 
|}
 
 
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!Type!!Gene/Region/Other
 
!Type!!Gene/Region/Other
 
|-
 
|-
−
|Concomitant Mutations||<span class="blue-text">EXAMPLE:</span> IDH1 R123H
+
|Concomitant Mutations||EXAMPLE IDH1 R123H
 
|-
 
|-
−
|Secondary Mutations||<span class="blue-text">EXAMPLE:</span> Trisomy 7
+
|Secondary Mutations||EXAMPLE Trisomy 7
 
|-
 
|-
−
|Mutually Exclusive||<span class="blue-text">EXAMPLE:</span> EGFR Amplification
+
|Mutually Exclusive||EXAMPLE 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. Do not delete table.'')</span>
+
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
+
|EXAMPLE: BRAF and MAP2K1; Activating mutations
−
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
+
|EXAMPLE: MAPK signaling
−
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
+
|EXAMPLE: Increased cell growth and proliferation
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
+
|EXAMPLE: CDKN2A; Inactivating mutations
−
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
+
|EXAMPLE: Cell cycle regulation
−
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
+
|EXAMPLE: Unregulated cell division
 
|-
 
|-
−
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
+
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
−
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
+
|EXAMPLE:  Histone modification, chromatin remodeling
−
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
+
|EXAMPLE:  Abnormal gene expression program
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification}}
+
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
  
 
None.
 
None.

Revision as of 14:46, 6 September 2024

Haematolymphoid Tumours (5th ed.)

editHAEM5 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).

(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). 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)

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.)

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
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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)

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
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  • 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 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)
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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

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.

None.

Genetic Diagnostic Testing Methods

  • Conventional chromosome analysis
  • FISH myeloid panel

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

Put your links here

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. ↑ 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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