Mixed-phenotype acute leukaemia, rare types
Haematolymphoid Tumours (5th ed.)
This page is under construction |
editHAEM5 Conversion NotesThis page was converted to the new template on 2023-11-03. The original page can be found at HAEM4:Mixed-Phenotype Acute Leukemia, Not Otherwise Specified (NOS), Rare Types.
Primary Author(s)*
Elicia Goodale, MD, Medical University of South Carolina
Daynna Wolff, PhD, Medical University of South Carolina
Cancer Category/Type
Acute Leukaemias of ambiguous lineage
Cancer Sub-Classification / Subtype
Mixed-phenotype acute leukaemia (MPAL), not otherwise specified, rare types
Definition / Description of Disease
In rare documented cases of leukemia, blasts may show clear features of biphenotypic leukemia (both T-cel and B-cell lineage) or even trilineage (also includes myeloid lineage). The European Group for the Immunological Characterization of Leukemias (EGIL) provides these criteria, which may provide for overestimation of dual lineage based on CD79a expression. CD79a and CD10 "should not be considered evidence of B-cell differentiation...because CD79a can be detected in T-lymphoblastic leukaemia with some antibodies. Ultimately, very little is known regarding clinical features and prognosis due to the rarity of the disease.
If erythroid and megakaryocytic lineages are the earliest branch points from pluripotency, as has been speculated, then T-cell, B-cell, and myeloid lineages have the greatest neoplastic potential. It would be possible for undetected erythroid or megakaryocytic lineages to occur, as they would not express MPO.[1]
Synonyms / Terminology
Mixed-phenotype acute leukaemia (MPAL), not otherwise specified, rare types should be distinguished from Mixed-phenotype acute leukaemia (MPAL), B/myeloid, not otherwise specified and from Mixed-phenotype acute leukaemia (MPAL), T/myeloid, not otherwise specified.[1]
Epidemiology / Prevalence
See Definition.
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.Median age: 45 years old[2]
Peripheral blood: 34% blasts[2]
Bone marrow: 84% blasts[2]
Complex karyotype is expected.[2]
Sites of Involvement
Bone Marrow
Morphologic Features
Immunophenotype is most important for this diagnosis.[1]
Immunophenotype
MPAL, not otherwise specified, should reveal clear elements of both B-cell lineage and T-cell lineage.[1]
Finding | Marker |
---|---|
Positive (T-cell component) | CD3, cCD3 |
Positive (B-cell component) | Strong CD19 + at least 1 of: CD10, cCD79a, CD22 |
Positive (B-cell component) | Weak CD19 + at least 2 of: CD10, cCD79a, CD22 |
Positive (myeloid component) | cMPO |
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.It should be noted that the classification of MPAL excludes cases that can be otherwise categorized, such as recurrent t(8;21), inv(16), or PML-RARA.[1]
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)
Unclear due to rarity of disease.
Venetoclax and Decitabine have been used to treat MPAL, T/myeloid, NOS, with some success.[3]
Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine) followed by SCT has been used to treat one B/T MPAL patient in a study.[3]
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.See Genes and Main Pathways Involved.
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.Not reported.
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.See Genes and Main Pathways Involved.
Epigenomic Alterations
Chromatin regulation via the ASXL1 gen is seen in over 20% of MPAL, B/myeloid, not otherwise specified and in over 10% of MPAL, T/myeloid, not otherwise specified.[4]
Methylation via the DNMT3A gene and IDH2 gene is affected in over 30% of MPAL, T/myeloid, not otherwise specified.[4]
Methylation via the IDH1 and TET2 genes is affected in over 15% of MPAL, B/myeloid, not otherwise specified, but in 0% of MPAL, T/myeloid, not otherwise specified.[4]
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 NOTCH1 pathway is mutated in 50% of MPAL, T/myeloid, not otherwise specified.[4]
RNA splicing (SRSF2) is mutated in over 20% of MPAL, B/myeloid, not otherwise specified.[4]
The RTK-RAS pathway, via FLT3 and NRAS genes, is mutated in a over 20% of MPAL, B/myeloid, not otherwise specified.[4]
Transcription factor pathways, via RUNX1, is mutated in a over 45% of MPAL, B/myeloid, not otherwise specified.[4]
Transcription factor pathways, via PHF6, is mutated in a over 20% of MPAL, T/myeloid, not otherwise specified.[4]
Genetic Diagnostic Testing Methods
Immunophenotype is essential. Based on newer information, genetic mutation profile may also help.[4][1]
Familial Forms
Not currently reported.
Additional Information
Links
Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "http://www." portion.)
References
- Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.
- Quesada AE, Hu Z, Routbort MJ, et al. Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing. Oncotarget. 2018;9(9):8441-8449. Published 2018 Jan 3. doi:10.18632/oncotarget.23878.
- Takahashi, K., Wang, F., Morita, K. et al. Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nat Commun 9, 2670 (2018). https://doi.org/10.1038/s41467-018-04924-z
- Heather Klocke, Zhao Ming Dong, Craig O’Brien, Nicholas Burwick, Robert E. Richard, Daniel Y. Wu, Thomas R. Chauncey, Solomon A. Graf, "Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)", Case Reports in Hematology, vol. 2020, Article ID 8811673, 4 pages, 2020. https://doi.org/10.1155/2020/8811673
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.
- ↑ 2.0 2.1 2.2 2.3 Quesada AE, Hu Z, Routbort MJ, et al. Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing. Oncotarget. 2018;9(9):8441-8449. Published 2018 Jan 3. doi:10.18632/oncotarget.23878. Notes
- ↑ 3.0 3.1 Heather Klocke, Zhao Ming Dong, Craig O’Brien, Nicholas Burwick, Robert E. Richard, Daniel Y. Wu, Thomas R. Chauncey, Solomon A. Graf, "Venetoclax and Decitabine for T/Myeloid Mixed-Phenotype Acute Leukemia Not Otherwise Specified (MPAL NOS)", Case Reports in Hematology, vol. 2020, Article ID 8811673, 4 pages, 2020. https://doi.org/10.1155/2020/8811673
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Takahashi, K., Wang, F., Morita, K. et al. Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nat Commun 9, 2670 (2018). https://doi.org/10.1038/s41467-018-04924-z
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, rare types”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/3/2023, https://ccga.io/index.php/HAEM5:Mixed-phenotype_acute_leukaemia,_rare_types.