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Acute leukemias of ambiguous lineage: diagnostic consequences of the WHO2008 classification

Leukemia volume 24, pages 1392–1396 (2010)Cite this article

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Acute leukemias (AL) are classified according to their commitment to either the myeloid or lymphoid lineage. Immunophenotyping for various intra- and extracellular cell lineage-specific markers is an important feature in differentiating between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). In about 4% of AL cases it is not clear whether blasts are derived from myeloid or lymphoid progenitors and are classified as AL of ambiguous lineage. AL with biphenotypic characteristics represent a subgroup with a worse prognosis, which can be partly explained by a higher incidence of the Philadelphia chromosome or other complex cytogenetic aberrancies; these patients present more often with extramedullar localization of disease, which urges for more intensive treatment protocols including central nervous system prophylaxis. The question whether these patients benefit from an (intensified) ALL or AML protocol is still unresolved due to lack of solid randomized treatment protocols.1, 2, 3, 4, 5

In 1995 the European group for immunological characterizing of AL (EGIL) presented guidelines for classification of AL with biphenotypic marker expression. These criteria were incorporated in the WHO2001 guidelines for classifying AL of ambiguous lineages. For many years the EGIL guidelines offered a platform for harmonizing diagnostic criteria important for prognosis and clinical outcome measurements.6, 7 In 2008 new WHO criteria were proposed for classification of acute leukemias of ambigious lineages.8 For acute leukemias with a mixed phenotype (MPAL), these new criteria implicated significant modification with the EGIL scoring system with potential implications for treatment and clinical research.8 For instance, in WHO2008 both bilineal and biphenotypic AL are classified as a MPAL, whereas these were distinct entities in the EGIL. Furthermore, single expression of cytoplasmatic myeloperoxidase (cytMPO) or CD3 (surface or intracellular) is now regarded as sufficient to determine whether blasts belong to the myeloid or T-cell lineage, respectively. AL that express both cytMPO and CD19 are now diagnosed as MPAL depending on the expression of cytCD79a, CD10 or cytCD22. In contrast to the EGIL, the WHO2008 excludes AL with certain cytogenetic aberrancies or clinical presentations from MPAL: AL with t(8;21), t(15;17) or inv(16) are classified as AML with recurrent cytogenetic abnormalities despite their immunophenotypic marker expression. Furthermore, AL with FGFR1 mutations, CML-blast crises, AL with MDS pre-phase and therapy-related AL are separate entities according to WHO2008 criteria.

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  1. Department of Hematology, Cancer Center Amsterdam, VU Institute for Cancer and Immunology, VU University Medical Center, Amsterdam, The Netherlands

    W van den Ancker, M Terwijn, T M Westers, P A Merle, A M Dräger, G J Ossenkoppele & A A van de Loosdrecht

  2. IT Department, VU University Medical Center, Amsterdam, The Netherlands

    E van Beckhoven

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  1. W van den Ancker
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  2. M Terwijn
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Correspondence to W van den Ancker.

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van den Ancker, W., Terwijn, M., Westers, T. et al. Acute leukemias of ambiguous lineage: diagnostic consequences of the WHO2008 classification. Leukemia 24, 1392–1396 (2010). https://doi.org/10.1038/leu.2010.119

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