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Leukemia - Acute

Other ALL

Ambiguous Lineage

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 28 September 2012, last major update September 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.


● Acute leukemias in which the morphologic, cytochemical and immuno-phenotypic features of the blasts:
      ● Lack sufficient evidence to classify as myeloid or lymphoid origin
      ● Or, have morphologic and/or immunophenotypic characteristics of both myeloid and lymphoid cells
      ● Or, have both B and T lineages (acute bilineal leukemia and acute biphenotypic leukemia)

Acute leukemias of ambiguous lineage include the following:
● Acute undifferentiated acute leukemia
● Mixed phenotype acute leukemia with t(9;22)(q34;q112.); BCR-ABL1
● Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
● Mixed phenotype acute leukemia, B/myeloid, NOS
● Mixed phenotype acute leukemia, T/myeloid, NOS
● Mixed phenotype acute leukemia, NOS rare types
● Other acute leukemias of ambiguous lineage


● <4% of all acute leukemias, more frequent in adults


● Unknown

Clinical features

● Related to bone marrow failure: fatigue, infections, bleeding


● Acute undifferentiated leukemia
      ● Leukemic cells lack any differentiating features
● Acute biphenotypic and acute bilineal leukemias
      ● May present as one subtype of AML with features of ALL (B, T or B and T)


Undifferentiated acute leukemia:
● Leukemias lack specific lineage markers
● cCD79a, cCD22, CD3 and MPO
● Generally donít express more than one lineage-associated marker
● Often express HLA-DR, CD34, CD38, may express TdT and CD7

Bilineal acute leukemia
● Dual population of blasts, each with distinct lineage: positive for myeloid, lymphoid or B and T-cell markers (Leukemia 2007;21:2264)
● May evolve into biphenotypic acute leukemia (Atlas of Genetics and Cytogenetics)

Biphenotypic acute leukemia
● Blasts co-express myeloid and T or B lineage markers
● Or, concurrent B and T lineage markers
● Rarely co-express markers for myeloid, T and B lineages

● Co-expression of one or two cross-lineage (non specific) markers is not sufficient for biphenotypic leukemia; e.g. myeloid-antigen positive ALL or Lymphoid antigen-positive AML
● Lineage switch after therapeutic intervention
      ● Possible expansion of pre-existing minor population of blasts of different lineage following therapeutic suppression of the major population
      ● Possible lineage instability


● High degree of cytogenetic abnormalities
● 1/3 of cases have Ph chromosome
● t(4;11)(q21;q23) or 11q23, typically have CD10(Ė) precursor B lymphoid component
● T/myeloid biphenotypic or bilineal leukemia can have complex karyotypes

Cell of origin

● Multipotent progenitor stem cell


● Unfavorable, particularly in adults
● t(4;11) or Ph particularly unfavorable


● Usually aggressive chemotherapy or bone marrow transplant

Case reports

● 5 year old boy with t(9;17)(p11;q11) (Leuk Lymphoma 1997;25:179)
● 20 year old woman with myeloid, B cell and NK phenotype (Arch Pathol Lab Med 2003;127:E93)
● 80 year old man with blasts coexpressing CD79a and myeloid markers (Arch Pathol Lab Med 2003;127:356)
● Due to transformation of essential thrombocythemia (Am J Hematol 2006;81:624)

Micro images

Blood smears:

Child with t(4;11)(q21;q23) - small blasts are early B cell precursors that are CD10 negative,
large cells are monocyte precursors that are alpha naphthyl butyrate esterase+

Blasts have minimal cytoplasm, fine chromatin with 1+ prominent nucleoli

Bone marrow smears:

2 week old girl with t(4;11)(q21;q23) - lymphoblasts and monoblasts

2 week old girl with t(4;11)(q21;q23) - Large cells are monoblasts and promonocytes,
small cells are lymphoblasts with minimal cytoplasm and coarse chromatin

Myeloid features include Auer rod (fig 1A-asterisk) and myeloperoxidase staining (fig 1B)

Flow cytometry images

Biphenotypic acute leukemia with CD19 and myeloperoxidase coexpression (figure B)

Electron microscopy images

Monocytoid blast has folded nucleus and scattered small electron dense granules

Molecular / genetics description

● Many cases have IgH and TCR rearrangements or deletions

Differential diagnosis

● For biphenotypic acute leukemia
      ● Myeloid antigen positive ALL
      ● Lymphoid antigen positive AML
● For undifferentiated acute leukemia
      ● Minimally differentiated AML
      ● Unusual precursor-B-cell or T-cell ALL

End of Leukemia - Acute > Other ALL > Ambiguous Lineage

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