RAPID COMMUNICATION Expression of the ABL-BCR Fusion Gene in Philadelphia-Positive Acute Lymphoblastic Leukemia

W e have previously shown that the chimeric gene ABL-BCR, formed on the derivative chromosome 9q + as a result of the t(9;22) translocation, is transcriptionally active in 65% of chronic myeloid leukemia patients. W e have now used the same technique, reverse transcription/polymerase chain reaction amplification of ABL-BCR transcripts, to study nine patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL); seven expressed the P190 and two the P210 type of BCR-ABLfusion protein. All seven patients with P I 90 had ABL-BCR transcripts containing a HE RECIPROCAL translocation t(9;22)(q34; q l 1) that T produces the Philadelphia (Ph) chromosome charac-teristic of chronic myeloid leukemia (CML) is also found in 2 % to 10 % of children and 20 % to 55 % of adults with acute lymphoblastic leukemia (ALL). The Ph chromosome car-ries a hybrid BCR-ABL gene thought to be central to the malignant process. In CML and in approximately 30 % of Ph+ ALLs, the break in the BCR gene occurs in the major breakpoint cluster region (M-bcr), and the BCR-ABL mRNA transcripts are formed by the junction of BCR exons b2 and/ or b3 to ABL exon 2 (b2a2 and b3a2, respectively). This results in a BCR-ABL protein of 210 Kd molecular weight (P210). In the remaining 70 % of Ph+ ALL patients, the breakpoints on chromosome 22 are more 5 ’ and cluster within the long first intron of the BCR gene, designated minor bcr (m-bcr). In these cases, only the first BCR exon is fused to ABL exon 2 (ela2 junction), and a smaller BCR-ABL protein of 190 Kd (P190) is formed. Because the t(9;22) is a reciprocal event, it could give rise to a second fusion gene, ABL-BCR, on the derivative 9q+. Such a gene should encode a protein containing the N-ter-minal ABL and C-terminal BCR domains that are absent from BCR-ABL, in a novel and perhaps functional fusion rearrangement. We have recently shown that the ABL-BCR fusion gene is in fact formed and transcribed in approximately two-thirds of CML patients3 We report here that ABL-BCR is also expressed in Ph+ ALL, and could encode fusion pro-teins with different functional domains depending on the breakpoint location in BCR