Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0-2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.

Induction of apoptosis in leukemic cell lines treated with captopril, trandolapril and losartan: a new role in the treatment of leukaemia for these agents.

Renin-angiotensin system (RAS) in the bone marrow is related to proliferation and cellular differentiation. We investigated the effect of ACE inhibitors (ACEI) captopril (>1mM) and trandolapril (>0.05 mM) and losartan (0.2 mM) on K562 cell line and K562 transfected with c-myc, bcl-x and bcl-2 (KmycB, Kbclx and Kbcl2 respectively). RAS components, proliferation, apoptosis and c-myc expression were analyzed. ACEI and losartan inhibited cell growth, decreased c-myc expression and increased apoptosis. These effects seem to be associated to angiotensin II-induced Smad activation. This work offers a new possible line of treatment for some acute myeloid leukemias and a new area of clinical research.