THE ABL BCR FUSION GENE ON CHROMOSOME-9 IN PH-NEGATIVE CHRONIC MYELOGENOUS LEUKEMIA - A CASE FOR VIGILANCE IN FLUORESCENCE IN-SITU HYBRIDIZATION INTERPRETATION/

We report cytogenetic, fluorescence in situ hybridization FISH), and m olecular analysis in a case of Ph-negative chronic myelogenous leukemi a patient with ABL/BCR fusion gene on chromosome 9 and a disparate FIS H signal pattern using two commercially available bcr/abl probes [Vysi s, Inc. and Oncor, Inc.). Cytogenetic analysis revealed a 46,XX normal female karyotype. FISH studies using Vysis LSI bcr/abl probe in inter phase cells demonstrated a BCR/ABL fusion pattern, similar to that of m-BCR/ABL fusion found in acute lymphoblastic leukemia. However, exami nation of metaphases revealed the ABL/BCR fusion signal on one of the chromosomes 9, an ABL signal on the other chromosome 9, and two BCR si gnals of different sizes on each of the chromosomes 22. Subsequently, a FISH study with the Oncor major (M)-bcr/abl translocation probe conf irmed the ABL/BCR fusion signal on chromosome 9 in addition to an ABL signal and a BCR signal located on chromosomes 9 and 22, respectively. Molecular studies (RT-PCR) revealed a rearrangement of the M-BCR regi on and expression of a chimeric bcr/abl mRNA of b3a2 configuration. Th is case suggest that it is imperative to have a full understanding of both the capabilities and the limitations of bcr/abl translocation pro bes and that FISH interphase signals should be confirmed on metaphase spreads for accurate diagnosis. (C) Elsevier Science Inc., 1998.