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Introduction:The evolution of making diagnosis of acute leukemia has seen many phases. Thediagnostic phases were-First was Morphology(M), second were cytochemistry, thencame the Flow cytometry/ immunophenotyping(I), then has been the phase of thecytogenetic(C) and molecular markers ex.FISH,PCR (M). Now the diagnosis of leukemia

will enter the phase of Gene sequencing profiling with microchips.The proponents of MIC and MICM have helped the development of WHO classificationof acute leukemia where diagnosis and prognosis have been incorporated.Medicine is going from phase of just making a diagnosis to phase of knowing which

patient will respond better or worse thats the prognosis. So does hemato-oncology wheremany entities have been associated wit poorer prognosis; so to say they respond poorly toconventional strategies of chemotherapy or require consolidation step most probably withtypes of Stem cell transplant.We hematologist have to think about the most non-toxic,cost-effective but effectivemethod for reducing the disease(from putting disease into remission to bringing down theMRD and then maintaining the state for as long as possible).

Now take example of Bi-phenotypic leukaemia. As if we hadnt had enough with oneheaded devil of ALL or AML that we have a double headed monster. Now I would take you through the analysis of this double headed monster by answeringsome questions like-How common is the problem?What is the evolution of disease?What are the tools to diagnose this problem?How do we classify so as to diagnose and prognosticate ?How do we treat?

How common is the problem?

With the advent of extensive immunophenotyping, acute lymphoblastic leukemias(ALLs) and acute myeloid leukemias (AMLs) that express cross-lineage antigens,the so-called lineage infidelity or lineage promiscuity, are not uncommon.1 However,most of these crosslineage antigen expressions are regarded as either ALLwith myeloid markers or AML with lymphoid markers. To unify the definition of

biphenotypic acute leukemia (BAL) for future multinational cooperative studies, theEuropean Group for Immunological Characterization of Leukemias proposed a scoringsystem, weighing on the degree of lineage specificity of each antigen. Following thesestringent criteria, BAL accounts for 4% to 8% of adult and pediatric acute leukemia.

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What is the evolution of disease?The normal hematopoesis in simplified way has following steps:

The stem cells have multiple functions which have been summarized:

STEM CELL

PROGENITOR

STEM CELL APOPTOSIS

G0

SELF-RENEWAL

DIFFERENTIATION

Any problem with differentiation and preserved self renewal with decreased apoptosisleads to acute leukemia. When the leukemia differentiates along a well defined lineage,then acute lymphoid or myeloid leukemia result. But when a malignancy involves more

primitive progenitor and the differentiation is promiscuous or under influence of cytokines which lead to confusing influence on the multipotent progenitor leading toarrest at a stage of differentiation which gives phenotype of both lineages on the blasts.

Now there are situations when the disease may differentiate along two lineagesdepending upon the cytokines in milieu. So these are called bi-lineal leukemia.

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1.Acute Leukemia With Myeloid, B-, and Natural Killer Cell DifferentiationA Novel Form of Multilineage Leukemia Po-Shing Lee, MD et al, Arch Pathol LabMed. 2003;127:e93e95