This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahmad, I. Articles by Mohammad, R. M. Search for Related Content PubMed PubMed Citation Articles by Ahmad, I. Articles by Mohammad, R. M.

Sequential Treatment of a Resistant Chronic Lymphocytic Leukemia Patient with Bryostatin 1 Followed by 2-Chlorodeoxyadenosine: Case Report¹

Department of Medicine, Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201

Bryostatin 1 (Bryo-1) has been shown to differentiate chronic lymphocytic leukemia (CLL) cells to the hairy cell leukemia phenotype. The purine analogue 2-chlorodeoxyadenosine (2-CdA) exhibits enhanced activity in patients with hairy cell leukemia compared to those with CLL. Here we present a case report of a patient diagnosed with resistant CLL and treated sequentially with Bryo-1 followed by 2-CdA for three cycles. Molecular and biochemical parameters relative to the sequential treatment with these agents in vivo were comparable to those found in the WSU-CLL cell line in vitro (R. M. Mohammad et al., Clin. Cancer Res., 4: 445–453, 1998; R. M. Mohammad et al., Biol. Chem., 379: 1253–1261, 1998). There was a significant reduction of lymphocyte count from 37.1 x 10³/µl before the treatment to 3.4 x 10³/µl after treatment, and partial remission was achieved 2 months after the treatment. The percentage of morphologically differentiated lymphocytes was increased from 3% before treatment to 92% with the first cycle of Bryo-1. Similarly, expression of CD22, a marker of differentiation, increased from 38% to 97% and was maintained at a high level for the duration of the treatment. Analysis of the molecular markers of apoptosis in isolated peripheral blood lymphocytes revealed an increase in the Bax:Bcl-2 ratio after treatment with Bryo-1 in cycles 2 and 3, with associated poly(ADP-ribose) polymerase cleavage after Bryo-1 and 2-CdA treatment. The deoxycytidine kinase:cytosolic 5'-nucleotidase activity ratio increased modestly after Bryo-1 treatment, indicating increased sensitivity of the peripheral blood lymphocytes to 2-CdA. In summary, we found that sequential treatment with Bryo-1 and 2-CdA caused a significant reduction in peripheral blood lymphocytes (CLL cells) with simultaneous induction of differentiation and the initiation of the Bax:Bcl-2 apoptotic pathway.

This article has been cited by other articles:

				T. E. Battle and D. A. Frank STAT1 mediates differentiation of chronic lymphocytic leukemia cells in response to Bryostatin 1 Blood, October 15, 2003; 102(8): 3016 - 3024. [Abstract] [Full Text] [PDF]