HAEM4Backup:Mixed Phenotype Acute Leukemia (MPAL), B/Myeloid, Not Otherwise Specified
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
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)
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].
Characteristic Chromosomal Aberrations / Patterns
NA
Genomic Gain/Loss/LOH
NA
Gene Mutations (SNV/INDEL)
NA
Other Mutations
NA
Epigenomics (Methylation)
Unknown. Methylation status is not determined for this subtype of MPAL.
Genes and Main Pathways Involved
The molecular data on B/Myeloid MPAL NOS are very scant and limited
Diagnostic Testing Methods
Diagnosis rests on immunophenotypic features. Flow cytometry and immunohistochemistry are the methods of choice.
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
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.
Familial Forms
Unknown
Other Information
NA
Links
Acute Leukemias of Ambiguous Lineage
References
- ↑ 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
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