Chronic myelogenous leukaemia with p185(BCR/ABL) expression: characteristics and clinical significance

We investigated the significance of p185(BCR/ABL). expression in patients w ith chronic myelogenous leukaemia (CML) in relation to disease features, th erapy and outcome. Results of Western blot analysis for 1384 patients refer red with a diagnosis of CML to our institution from 1989 to 1997 were revie wed, Clinical characteristics, results of cytogenetic analysis and RT-PCR f or BCR rearrangement were analysed. Five patients with Ph-positive CML expr essing the p185(BCR/ABL) hybrid protein were identified. By RT-PCR, bone ma rrow specimens of these patients were confirmed to have an e1a2 junction. T he median age at diagnosis of these patients was 55 years (range 43-76). Al l had elevated white cell counts at diagnosis (median 50x10(9)/1. range 11. 7-163x10(9)/1). Four patients had monocytosis (range 10-16%) with a low neu trophil/monocyte ratio in the peripheral blood (range 3.4-5.7). Patients pr esented with various stages of the disease (two in chronic-phase CP, two in accelerated-phase AP, and one in blastic-phase BP). The clinical course an d therapy of the patients varied, with one patient receiving hydroxyurea on ly three patients receiving hydroxyurea followed by interferon-alpha based regimens and bone marrow transplantation. The patient presenting in BP was treated with combination chemotherapy The clinical outcome of the patients was also varied with one patient alive and in complete remission (with comp lete cytogenetic remission after transplant) and four patients dead after p rogression to more advanced stages. We conclude that patients with Ph-positive p185(BCR/ABL) CML frequently pre sent with monocytosis and a low neutrophil/monocyte ratio in the peripheral blood, aiding the speculation that the presence of the p185(BCR/ABL) hybri d protein may contribute to a phenotype intermediate between CML and CMML. Of interest, the only other specific clinical feature identified was the ab sence of splenomegaly in four of five patients. There was no definite assoc iation with transformation to lymphoid blast phase.