Mixed-phenotype acute leukaemia, T/myeloid

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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:Mixed Phenotype Acute Leukemia (MPAL), T/Myeloid, Not Otherwise Specified.

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Primary Author(s)*

Narsis Attar, MD, PhD, Fabiola Quintero-Rivera, MD University of California, Irvine

Cancer Category / Type

Acute leukemia

Acute leukemias of ambiguous lineage

Cancer Sub-Classification / Subtype

Mixed-phenotype acute leukemia (MPAL), T/myeloid, not otherwise specified (NOS)

Definition / Description of Disease

This malignancy is defined as a distinct entity in the WHO classification as a subtype of mixed-phenotype acute leukemia (MPAL). It fulfills the criteria for both T-cell and myeloid lineage and requires the absence of genetic mutations associated with other MPAL subtypes (e.g. KMT2A or BCR-ABL1 rearrangement)[1].

Synonyms / Terminology

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Epidemiology / Prevalence

A rare entity accounting for <1% of all leukemias. It is seen both in adult and pediatric populations.

Clinical Features

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Signs and Symptoms EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)


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.

Patient with mixed-phenotype acute leukemia, T/myeloid, NOS present with signs and symptoms similar to other acute leukemias including an elevated white blood cell count.

Sites of Involvement

Bone marrow

Morphologic Features

Blasts with no distinguishing features resembling lymphoblastic leukemia OR a dimorphic blast population with some resembling lymphoblasts and others myeloblasts[1].


Put your text here and fill in the table (Instruction: Can include references in the table)

Finding Marker
Positive (universal) EXAMPLE CD1
Positive (subset) EXAMPLE CD2
Negative (universal) EXAMPLE CD3
Negative (subset) EXAMPLE CD4

The content below was from the old template. Please incorporate above.

The blasts must meet criteria for both T-cell and myeloid lineage assignment.

According to the WHO, T-cell assignment is defined as having cytoplasmic CD3 (using antibody to CD3 epsilon chain). The European Group for the Immunological Characterization of Leukemias (EGIL) criteria also includes CD7, CD5 and CD2. The WHO myeloid lineage assignment requires MPO expression (by flow cytometry, immunohistochemistry or cytochemistry) or monocytic differentiation with 2 of the following CD11c, CD14, CD64, lysozyme, non-specific esterase. The EGIL criteria also considers CD13, CD33 and CD117 (c-kit), among a number of other markers that are variably weighted, in defining the myeloid lineage[1][2][3].   

Chromosomal Rearrangements (Gene Fusions)

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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)


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)
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Must lack t(v;11q23.3); KMT2A rearrangement and t(9;22)(q34.1;q11.2); BCR-ABL1 rearrangement   

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)

Prognosis: Although data is limited, MPAL T-myeloid, NOS is considered to have a poor prognosis.

Treatment: Retrospective studies suggest higher rates of complete remission and at least equivalent overall survival with ALL-therapy regimen compared with AML therapy. Allogeneic hematopoietic stem cell transplantation is utilized and may be effective in MPAL[4][5][6]. High quality prospective studies are needed to determine the optimal therapy for MPAL.

Individual Region Genomic Gain / Loss / LOH

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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



chr7:1- 159,335,973 [hg38]




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).




chr8:1-145,138,636 [hg38]




Common recurrent secondary finding for t(8;21) (add reference).

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

Co-deletion of 1p and 18q


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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Clonal chromosomal abnormalities including complex karyotypes are observed in the majority of cases but no specific aberration or pattern has been assigned to this leukemia[7][8].

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


EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations


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.

MPALs with T-lineage differentiation are more often found to have either PHF6 or DNMT3A mutations[9]. Genetic lesions in NOTCH1 have also been reported in a subset of cases and are thought to be exclusively associated with T/myeloid MPAL. The overall mutational burden may be higher in MPALs with T-lineage differentiation[8][9][10].

Epigenomic Alterations

Methylation status is not determined for this subtype of MPAL. Mutations in epigenetic regulatory genes (DNMT3A, IDH2, EZH2, WT1, RUNX1, ETV6, and ASXL1) have been reported in MPAL with T/myeloid phenotype[9][10]. Of note, DNMT3A mutations were observed in 33% of adult MPAL patients[10].

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

Genetic Diagnostic Testing Methods

Diagnosis rests on immunophenotypic features. Flow cytometry and immunohistochemistry are the methods of choice.

Familial Forms

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Additional Information

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  1. 1.0 1.1 1.2 Borowitz MJ, et al., (2017) Acute leukaemias of ambiguous lineage, in WHO 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, p185-186.
  2. 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. Charles, Nathan J.; et al. (2017). "Mixed-Phenotype Acute Leukemia: Diagnostic Criteria and Pitfalls". Archives of Pathology & Laboratory Medicine. 141 (11): 1462–1468. doi:10.5858/arpa.2017-0218-RA. ISSN 1543-2165. PMID 29072953.
  4. Maruffi, Maria; et al. (2018). "Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis". Leukemia. 32 (7): 1515–1528. doi:10.1038/s41375-018-0058-4. ISSN 1476-5551. PMID 29550836.
  5. Liu, Qi-Fa; et al. (2013). "Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens". Annals of Hematology. 92 (5): 679–687. doi:10.1007/s00277-012-1662-4. ISSN 1432-0584. PMID 23274355.
  6. Shimizu, Hiroaki; et al. (2015). "Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis". European Journal of Haematology. 95 (5): 455–460. doi:10.1111/ejh.12516. ISSN 1600-0609. PMID 25605541.
  7. 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.
  8. 8.0 8.1 Matutes, Estella; et al. (2011). "Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification". Blood. 117 (11): 3163–3171. doi:10.1182/blood-2010-10-314682. ISSN 1528-0020. PMID 21228332.
  9. 9.0 9.1 9.2 Xiao, Wenbin; et al. (2018). "PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation". Blood Advances. 2 (23): 3526–3539. doi:10.1182/bloodadvances.2018023531. ISSN 2473-9537. PMC 6290101. PMID 30530780.
  10. 10.0 10.1 10.2 Eckstein, Olive S.; et al. (2016). "Mixed-phenotype acute leukemia (MPAL) exhibits frequent mutations in DNMT3A and activated signaling genes". Experimental Hematology. 44 (8): 740–744. doi:10.1016/j.exphem.2016.05.003. ISSN 1873-2399. PMC 4956537. PMID 27208809.


*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, T/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,_T/myeloid.