Bone marrow neoplastic
Bone marrow - plasma cell and lymphoid neoplasms
Acute leukemia of ambiguous lineage
Mixed phenotype


Topic Completed: 1 September 2012

Minor changes: 19 June 2020

Copyright: (c) 2001-2020, PathologyOutlines.com, Inc.

PubMed Search: Mixed phenotype acute leukemia MPAL


Page views in 2019: 958
Page views in 2020 to date: 1,160
Cite this page: Mihova D. Mixed phenotype. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiamixedpheno.html. Accessed November 23rd, 2020.
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)

Excludes:
  • 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:

Contributed by Daniela Mihova, MD
Missing Image

The European Group for the Immunological Classification of Leukemias (EGIL) scoring system


Missing Image

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

Morphology:
  • 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
Missing Image

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

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

Genetics:
  • 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)
Back to top
Image 01 Image 02