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

We investigated the significance of p185(BCR/ABL) expression in patients with chronic myelogenous leukaemia (CML) in relation to disease features, therapy and outcome. Results of Western blot analysis for 1384 patients referred with a diagnosis of CML to our institution from 1989 to 1997 were reviewed. Clinical characteristics, results of cytogenetic analysis and RT- PCR for BCR rearrangement were analysed. Five patients with Ph-positive CML expressing the p185(BCR/ABL) hybrid protein were identified. By RT-PCR, bone marrow specimens of these patients were confirmed to have an ela2 junction. The median age at diagnosis of these patients was 55 years (range 43-76). All had elevated white cell counts at diagnosis (median 50 x 10⁹/l, range 11.7- 163 x 10⁹/l). Four patients had monocytosis (range 10-16%) with a low neutrophil/monocyte ratio in the peripheral blood (range 3.4-5.7). Patients presented 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 and therapy of the patients varied, with one patient receiving hydroxyurea only, three patients receiving hydroxyurea followed by interferon-α 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 complete cytogenetic remission after transplant) and four patients dead after progression to more advanced stages. We conclude that patients with Ph- positive p185(BCR/ABL) CML frequently present with monocytosis and a low neutrophil/monocyte ratio in the peripheral blood, aiding the speculation that the presence of the p185(BCR/ABL) hybrid protein may contribute to a phenotype intermediate between CML and CMML. Of interest, the only other specific clinical feature identified was the absence of splenomegaly in four of five patients. There was no definite association with transformation to lymphoid blast phase.