Mixed-phenotype acute leukaemia, B/myeloid
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis 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.
(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)*
Priyatharsini Nirmalanantham, MD and Shashi Shetty, PhD
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | Myeloid proliferations and neoplasms |
| Family | Acute leukaemias of mixed or ambiguous lineage |
| Type | Acute leukaemia of ambiguous lineage, immunophenotypically defined |
| Subtype(s) | Mixed-phenotype acute leukaemia, B/myeloid |
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. 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 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. 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/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. 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 / 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 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)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. Do not delete 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
(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.)
- ↑ 1.0 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 09/6/2024, https://ccga.io/index.php/HAEM5:Mixed-phenotype_acute_leukaemia,_B/myeloid.