Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the progression of chronic myelogenous leukemia from diagnosis to blastic phase.

Chronic myelogenous leukemia (CML) has a progressive course but little is known about the biologic characteristics of disease progression. This study was designed to assess the changes in cell proliferative characteristics, apoptosis, the expression of the bcl-2 and c-myc genes between the time of initial diagnosis and entrance into the blastic phase of the disease. We observed that the rate of cell proliferation decreased and the cell death rate did not significantly change as the disease accelerated. The level of bcl-2 expression was significantly higher in accelerated/blastic phase cells than in the chronic phase cells in the population as a whole, however, the bcl-2 expression level did not change in blast cell subpopulation. c-myc Expression was significantly higher in the blast cell subpopulation of accelerated/blastic phase than in that of earlier phases of the disease. In conclusion, the characteristics of CML cells, namely proliferation rate, c-myc and bcl-2 change during the course of the disease. It is possible that the change in c-myc expression plays a causative role in evolution of the blastic phase from the chronic phase.

The effects of 13-cis retinoic acid and interferon-alpha in chronic myelogenous leukemia cells in vivo in patients.

The effects of the administration of a 3-day course of 13-cis retinoic acid in combination with interferon a [RA/IFN] on the leukemia cells was measured in vivo in 43 patients with chronic myelogenous leukemia. The administration of RA/IFN was associated with a significant fall in the white blood cell count of patients with chronic-phase disease and with a fall in the percentage S-phase cells in CML patients regardless of the stage of their leukemia. In two thirds of the patients studied the administration of RA/IFN was also associated with an increase in marrow apoptosis. The cytokine combination also suppressed bcl-2 and myc expression in a minority of patients and such expression appears to be associated with response to a treatment regimen which includes RA/IFN. These studies are the first to directly assess the effects of the combination of RA/IFN on chronic myelogenous leukemia cells in vivo in patients. These effects, if seen in other malignant diseases, could account for the therapeutic benefit which has been associated with the administration of this combination of biological agents to patients with malignant disease.

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic myeloid leukemia following radioactive iodine (131)I therapy of thyroid cancer.

We describe a 51 years old female patient who developed Ph(1) positive chronic myeloid leukemia 7 years following radioactive iodine therapy for follicular carcinoma of thyroid. Until now, only two patients have been reported to have developed CML after this kind of therapy. The underlying mechanisms are discussed and the need to study such patients at cytogenetic, molecular biologic and cell kinetic levels is stressed.