Faculty Collaboration Database

Significance and correlations of molecular analysis results in patients with Philadelphia chromosome-negative chronic myelogenous leukemia and chronic myelomonocytic leukemia. Am J Med 1988 Nov;85(5):639-44

Date

11/01/1988

Pubmed ID

3189367

DOI

10.1016/s0002-9343(88)80235-3

Scopus ID

2-s2.0-0024204183 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

PURPOSE: Several investigators have documented a rearrangement of the breakpoint cluster region (bcr) in selected patients with a morphologic diagnosis of chronic myelogenous leukemia (CML) but no abnormality of the Philadelphia chromosome (Ph) by cytogenetic studies. Our intention was to systematically investigate the incidence of the bcr rearrangement in such patients, and to correlate the findings with patient characteristics, response to therapy (especially alpha interferon treatment), and overall prognosis.

PATIENTS AND METHODS: Molecular analysis studies were performed in 40 patients with Ph-negative CML (23 patients) and myelomonocytic leukemia (CMML; 17 patients).

RESULTS: Rearrangement of the breakpoint cluster region (bcr) was detected in 11 of the 23 patients with Ph-negative CML (48 percent), indicating the presence of the abnormal molecular events in Ph-positive CML without documentation of the Ph cytogenetic abnormality. None of the 17 patients with CMML had the bcr rearrangement. Patients with Ph-negative CML and the bcr rearrangement had characteristics similar to those of patients with Ph-positive disease. These included a younger age, higher white blood cell counts, a higher incidence of thrombocytosis and basophilia, and a lower occurrence of thrombocytopenia. The leukocyte alkaline phosphatase score was not a helpful distinguishing feature. Among 21 patients receiving alpha interferon-based regimens, response to therapy was significantly better among patients with Ph-negative disease and the bcr rearrangement (seven of seven, 100 percent), compared with those without the bcr rearrangement (one of six, 17 percent), or patients with CMML (two of eight, 25 percent) (p less than 0.01). At this time of follow-up, only one of the 11 patients with Ph-negative CML and the bcr rearrangement had died from complications of allogeneic bone marrow transplantation, compared with three deaths among the 12 patients with Ph-negative CML and no bcr rearrangement, and 11 deaths among the 19 patients with CMML.

CONCLUSION: We conclude that molecular studies help in better understanding the nosology of Ph-negative CML, and define a subgroup of patients with clinical, therapeutic, and prognostic correlations similar to those of patients with Ph-positive CML.

Author List

Kantarjian HM, Shtalrid M, Kurzrock R, Blick M, Dalton WT, LeMaistre A, Stass SA, McCredie KB, Gutterman J, Freireich EJ

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Female
Gene Rearrangement
Humans
Immunoblotting
Interferon Type I
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Male
Middle Aged
Molecular Probes
Philadelphia Chromosome
Prognosis
Recombinant Proteins