Leukemia - Acute
Other ALL
Mixed phenotype acute leukemia (MPAL)

Topic Completed: 1 September 2012

Revised: 22 January 2019, last major update September 2012

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PubMed Search: Mixed phenotype acute leukemia MPAL

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Cite this page: Mihova D. Mixed phenotype acute leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiamixedpheno.html. Accessed November 14th, 2019.
Definition / general
  • De novo acute leukemia containing separate populations of blasts of more than one lineage (bilineal or bilineage), or a single population of blasts co-expressing antigens of more than one lineage (biphenotypic)

  • Acute myeloid leukemia (AML) with recurrent translocations t(8;21), t(15;17) or inv(16)
  • Leukemias with FGFR1 mutations
  • Chronic myelogenous leukemia (CML) in blast crisis
  • Myelodysplastic syndrome (MDS) related AML and therapy related AML, even if they have MPAL immunophenotype

Criteria for biphenotypic leukemia:
  • Score of 2 or more for each of two separate lineages (shown below)
Diagrams / tables

Images hosted on other servers:
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The European Group for the Immunological Classification of Leukemias (EGIL) scoring system

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2008 WHO classification of acute leukemias of ambiguous lineage

Prognosis and treatment
  • Poor, overall survival of 18 months
  • Young age, normal karyotype and ALL induction therapy are associated with favorable survival
  • Ph+ is a predictor for poor prognosis
  • Bone marrow transplantation should be considered in first remission
MPAL with t(9;22)(q34;q11.2); BCR-ABL1
  • 20% of all MPAL
  • Blasts with t(9;22)(q34;q11.2) translocation or BCR-ABL1 rearrangement (Ph+) without history of CML
  • Majority in adults
  • High WBC counts

  • Most of the cases B/myeloid phenotype
  • Rare T/myeloid, B and T lineage, or trilineage leukemias

  • Many cases show a dimorphic blast population, one resembling myeloblasts and the other lymphoblasts

Cytogenetic abnormalities:
  • Conventional karyotyping for t(9;22), FISH or PCR for BCR-ABL1 translocation
  • Additional complex karyotypes
  • Ph+ is a poor prognostic factor for MPAL with a reported median survival of 8 months
  • Worse than patients of all other types of MPAL
MPAL with t(v;11q23); MLL rearranged
  • Meeting the diagnostic criteria for MPAL with blasts bearing a translocation involving the 11q23 breakpoint (MLL gene)
  • MPAL with MLL rearranged rare
  • More often seen in children and relatively common in infancy
  • High WBC counts
  • Poor prognosis
  • Dimorphic blast population with one resembling monoblasts and the other resembling lymphoblasts
  • Lymphoblast population often shows a CD19+, CD10- B precursor immunophenotype, frequently CD15+
  • Expression of other B markers usually weak
  • Translocations involving MLL gene include t(4;11)(q21;q23), t(11;19)(q23;p13) and t(9;11)(p22;q23)
  • Cases with chromosome 11q23 deletion should not be classified in this category
Molecular / cytogenetics images

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t(4;11)(q21;23) in bilineal leukemia

MPAL B/Myeloid, NOS
  • Meets the diagnostic criteria for MPAL with both B and myeloid lineages without Ph+ and MLL rearrangement
  • B/myeloid acute leukemia accounts for 1% of all leukemias
  • More common in adults but also seen in children

  • Dimorphic populations, resembling lymphoblasts and myeloblasts, or a single population resembling ALL

  • Multiple different cytogenetic changes have been demonstrated, however none is proven to be specific in this subtype
MPAL T/Myeloid, NOS
  • Meets the diagnostic criteria for MPAL with both T and myeloid lineages without Ph+ and MLL rearrangement
  • More often in children, though in adults as well
  • Dimorphic populations, resembling lymphoblasts and myeloblasts, or a single population resembling ALL
  • Other commonly expressed T-lineage markers include CD2, CD7
  • Myeloid markers MPO, CD117, TdT, CD13 and CD33
  • T cell plus myeloid cases may have 2p13 translocations or other unrelated anomalies (Leukemia 2007;21:2264)
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