Mixed-phenotype acute leukaemia, B/myeloid
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Mixed Phenotype Acute Leukemia (MPAL), B/Myeloid, Not Otherwise Specified.
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Primary Author(s)*
Priyatharsini Nirmalanantham, MD and Shashi Shetty, PhD
Cancer Category / Type
Acute Leukemias of Ambiguous Lineage
Cancer Sub-Classification / Subtype
Mixed Phenotype Acute Leukemia (MPAL), B/Myeloid, Not Otherwise Specified
Definition / Description of Disease
The 2017 World Health Organization (WHO) classification of hematopoietic and lymphoid tumors[1] defines five subtypes of MPAL:
MPAL with t(9;22)(q34;q11.2)
- MPAL with MLL rearrangement
- MPAL B/myeloid not otherwise specified (NOS)
- MPAL T/myeloid NOS
- MPAL NOS
The term B/myeloid MPAL NOS refers to leukemia cases in which blasts express B-lymphoid and myeloid lineage markers (biphenotypic) or with multiple blast populations each expressing different lineage antigens (bi-lineal) or a combination of both. Importantly, B/myeloid MPAL NOS refers to MPAL cases without the t(9;22)(q34;q11.2)/BCR-ABL1 or the t(v;11q23)/MLL rearrangements.
Mixed-phenotype acute leukemia, B/myeloid, not otherwise specified, fulfills the criteria for B/myeloid leukemia, but does not fulfill the criteria for any of the genetically defined subgroups.
This page will focus specifically only on B/myeloid MPAL, NOS.
Synonyms / Terminology
Mixed lineage leukemia, bilineal leukemia, biphenotypic leukemia.
Mixed phenotype acute leukemia, B/myeloid, NOS
MPAL, B/myeloid, NOS
Leukemia, NOS
Acute undifferentiated leukemia
Myeloid leukemia, NOS
Acute myeloid leukemia, NOS
Epidemiology / Prevalence
Mixed phenotype acute leukemia (MPAL) accounts for 2-5% of all acute leukemias. B/myeloid MPAL NOS is a rare leukemia, accounting for less than 1% of all leukemia. It can occur in both children and adults. It make be more frequent in adults than is T/Myeloid MPAL[1].
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 FeaturesThe content below was from the old template. Please incorporate above.Patients present similarly to other patients with acute leukemia.
Sites of Involvement
Similar to other patients with acute leukemia.
Morphologic Features
The mixed-phenotype acute leukemias consist of morphologically homogeneous or heterogeneous blasts with a spectrum that includes lymphoid-appearing cells and myeloid-appearing cells. The lymphoid-appearing cells are small, with scant cytoplasm and condensed chromatin, often with absent or inconspicuous nucleoli. The myeloid-appearing cells are larger, with abundant cytoplasm, finely dispersed nuclear chromatin, and prominent nucleoli.
Immunophenotype
Finding | Marker |
---|---|
Positive (universal) | Myeloid lineage
- MPO (flow cytometry, immunohistochemistry, or enzyme cytochemistry) OR evidence of monocytic differentiation: with at least 2 of the following: non-specific esterase cytochemistry, CD11c, CD14, CD64, lysozyme. AND B-cell component - Strong CD19 with at least 1 of the following strongly expressed: CD79a, cytoplasmic CD22, or CD10 -OR Weak CD19 with at least 2 of the following strongly expressed: CD79a, cytoplasmic CD22, or CD10 |
Positive (subset) | MPO positive myeloblasts and monoblasts commonly also express other myeloid-associated markers:
CD13 CD33 CD117 B-cell component also expresses other B-cell markers: CD20 (rare)[2] |
Negative (universal) | NA |
Negative (subset) | NA |
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.Most cases have clonal chromosomal abnormalities, although none is frequent enough to suggest specificity for this group of leukaemias. There are insufficient data in the literature to determine whether B/myeloid and T/myeloid MPALs have different frequencies of various genetic lesions, once t(9;22) and KMT2A rearrangements have been counted for. Chromosome abnormalities reported in more than one case include chromosome 12p abnormalities, deletion 5q, deletion 6p, numerical abnormalities including near tetraploidy and structural abnormalities of chromosome 7 including deletion of IKZF1[3]. Complex karyotypes are common[4].
Gene expression profile suggest a signature intermediate between ALL and AML in most cases. Current literature on the genomic alterations in B/Myeloid MPAL appears to overlap extensively with ALL and AML including mutations in ASCL1, TET1, TET2, IDH1, IDH2, DNMT3A, NOTCH1 and ETV6[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)
B/myeloid MPAL, NOS is generally considered a poor-prognosis leukaemia, although data on the outcome of these cases vs. other MPALs are limited.
Currently there is no consensus regarding the optimal (AML- or ALL-directed) therapeutic regimen. In children, outcome is worse than that of ALL. In adults, outcome appear to be better than that of AML and no different than that of other ALLs. Patient with B/myeloid MPAL, NOS, have not been treated uniformly.
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/LOHThe content below was from the old template. Please incorporate above.NA
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 / PatternsThe content below was from the old template. Please incorporate above.NA
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.NA
Other Mutations
NA
Epigenomic Alterations
Unknown. Methylation status is not determined for this subtype of MPAL.
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 InvolvedThe content below was from the old template. Please incorporate above.The molecular data on B/Myeloid MPAL NOS are very scant and limited
Genetic Diagnostic Testing Methods
Diagnosis rests on immunophenotypic features. Flow cytometry and immunohistochemistry are the methods of choice.
Familial Forms
Unknown
Additional Information
NA
Links
HAEM4:Acute Leukemias of Ambiguous Lineage
References
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- ↑ 1.0 1.1 Borowitz MJ, et al., (2017). Acute leukemias of ambiguous lineage, in World Health Organization 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, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p184-185.
- ↑ Weir, E. G.; et al. (2007). "Acute bilineal leukemia: a rare disease with poor outcome". Leukemia. 21 (11): 2264–2270. doi:10.1038/sj.leu.2404848. ISSN 0887-6924. PMID 17611554.
- ↑ Owaidah, T. M.; et al. (2006). "Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system". Leukemia. 20 (4): 620–626. doi:10.1038/sj.leu.2404128. ISSN 0887-6924. PMID 16437134.
- ↑ Manola, Kalliopi N. (2013). "Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview". British Journal of Haematology. 163 (1): 24–39. doi:10.1111/bjh.12484. ISSN 1365-2141. PMID 23888868.CS1 maint: display-authors (link)
- ↑ Yan, Lingzhi; et al. (2012). "Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification". Haematologica. 97 (11): 1708–1712. doi:10.3324/haematol.2012.064485. ISSN 1592-8721. PMC 3487445. PMID 22581002.
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: “Mixed-phenotype acute leukaemia, B/myeloid”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Mixed-phenotype_acute_leukaemia,_B/myeloid.