BCR-ABL transcripts in philadelphia-negative myeloproliferative disorders

Philadelphia-negative (Ph-neg) essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF) form a syndrome of related chronic mveloproliferative disorders (MPD) characterized by expansion of one or more of the hematopoietic stem cells. A close relationship between the acquired dona) disorders of ET, PV and IMF and a progression of increasing abnormality in the stem cells from the least abnormal state in PV to intermediate abnormality in ET to the most abnormal state in MF has been suggested. Chimeric BCR-ABL transcript, arising from the chromosomal translocation t(9;22)(q34;ql 1.2), is a molecular anomaly which causes cytokine independent proliferation, induces tumorigenic growth and prevents apoptosis. Based on our previous finding of BCR-ABL- transcripts in bone marrow aspirâtes (BMA) of 48% of Ph-neg ET (a study of 25 patients), we think that molecular inspection of MPD group of patients (other than CML) is important for Ph-neg clinical evaluation and has implication on treatment modalities. i'his report is comprised of Ph-neg patients who met the polycythemia vera study group (PVSG) criteria. BMA and peripheral blood (PB) samples were subjected to reverse transcriptase two-step nested polymerase chain reaction (RT-PCR) and Southern blotting. Forty BMA of Ph-neg ET patients were analyzed, 48% were positive for BCR-ABL (58% carry b3a2 and 42% b2a2 rearrangement). In a preliminary study examining concordance or discordance of BCR-ABL expression in BMA and PB of Ph-neg ET patients, 4 cases out of i with BCR-ABL transcripts in BM, expressed it in their PB, while 3 were negative in PB. We examined PB of 18 ET patients (distinct from the group of 40 BMA analyzed), 17% expressed BCR-ABL transcripts in their PB. PB samples from 23 PV patients were examined, 13% of these were BCR-ABL positive, all expressed b2a2 transcripts. PB samples of 9 IMF patients were examined, 44% of who were positive. We have analyzed 6 BMA and 6 PB of volunteers and found them all negative for BCR-ABL transcripts. We suggest that the BCR-ABL status should be investigated in patients with MPD in a long follow-up period in order to understand the nature and significance of this observation.