Introduction: The evolution of making diagnosis of acute leukemia has seen many phases.

The diagnostic phases were-First was Morphology(M), second were cytochemistry, then came the Flow cytometry/ immunophenotyping(I), then has been the phase of the cytogenetic(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 classification of 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 where many entities have been associated wit poorer prognosis; so to say they respond poorly to conventional strategies of chemotherapy or require consolidation step most probably with types of Stem cell transplant. We hematologist have to think about the most non-toxic,cost-effective but effective method for reducing the disease(from putting disease into remission to bringing down the MRD and then maintaining the state for as long as possible). Now take example of Bi-phenotypic leukaemia. As if we hadnt had enough with one headed 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 answering some questions likeHow 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 ALL with myeloid markers or AML with lymphoid markers. To unify the definition of biphenotypic acute leukemia (BAL) for future multinational cooperative studies, the European Group for Immunological Characterization of Leukemias proposed a scoring system, weighing on the degree of lineage specificity of each antigen. Following these stringent criteria, BAL accounts for 4% to 8% of adult and pediatric acute leukemia.

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:
G0

STEM CELL APOPTOSIS

SELF-RENEWAL

STEM CELL

DIFFERENTIATION

PROGENITOR

Any problem with differentiation and preserved self renewal with decreased apoptosis leads 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 to arrest 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 lineages depending upon the cytokines in milieu. So these are called bi-lineal leukemia.

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