Frequent retinoic acid receptor alpha (Rar-alpha) gene rearrangements and no point mutations of N-Ras gene in fifteen cases of acute promyelocytic leukemia.
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Biomedical subjects
Publications and source records attributed to J Sánchez-Fayos.
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PURPOSES: To analyze the reproducibility to detect the t (15; 17) with molecular and cytogenetic techniques. PATIENTS AND METHODS: Fifteen cases of acute promyelocytic leukaemia were studied by means of cytogenetic techniques (GTG banding) and molecular ones (K/S probe and HindIII, EcoRI and BamHI restriction enzymes). RESULTS: The t (15; 17) was detected with cytogenetic techniques in 60% cases and with molecular ones in 33% cases. Using both (cytogenetic and molecular) techniques the translocation was detected in 73% cases. CONCLUSIONS: The use of both techniques may be very useful in order to get a better diagnostic and a closer control of the patient's clinical evolution.
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For the last 13 years, 47 patients with ALL over 15 years old (range 15-72; median 21) entered a 'total-therapy' programme. All cases received a 6-8 week induction course of PRD, VCR, DRB and/or L-ASN. Prophylaxis of CNS was done by cranial radiotherapy plus i.t. MTX in 32/45 patients who attained complete remission (CR). After CR, subsequent therapy involved a programme of maintenance with 6MP and MTX at full doses. Pulses of intermittent reinforcement (PRD, VCR and DRB) were done for 2 weeks, every 3 months, for at least 3 years. CR was achieved in 42/47 patients (89.3%). The median relapse-free survival of the patients who attained CR was 57 months, with an 8-year estimated disease-free survival rate of 43% for those cases. If actuarial assumptions were to be sustained, it would indicate an encouraging cure rate of 38% of all our adult ALL patients (mainly in those cases between 15 and 30 years old).
We report a clinical hematologic sequential process consisting of transient marrow aplasia post-hepatitis (non A-non B) preceding acute lymphoblastic leukemia. There have not been other reports mentioning a similar evolution. Authors outline the possible pathogenetic mechanisms involved in the sequence of events described. We suggest that viral infection produces a lesion of the stem-cell which could have different expressions depending on the stages of the disease at which it is studied. Those varied expressions perhaps could be explained by the modulation induced by the host's immunologic system.
Kinetic studies of marrow dividing granulocytic precursors (mitotic index and flash labeling index with 3H-TDR) were carried out in 11 patients with oligoblastic leukemia (OBL). The results were compared with similar data from cases of conventional acute non-lymphocytic leukemia (ANLL). The cytokinetic results were as follows: MI (%) in OBL, mean = 0.75; MI (%) in ANLL, mean = 0.66; p greater than 0.7; LI (%) in OBL, mean = 15.0; LI (%) in ANLL, mean = 15.4, p greater than 0.7. The lack of cytokinetic differences between these two groups of patients stands in favor of the hypothesis that OBL might represent a special type of smoldering leukemia with a 'plateau' of blast cell accumulation established at a subleukemic level.
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Kinetic studies of leukemic blast cells (LBC) and erythroblasts were carried out in 20 cases of acute myeloblastic leukemia (AML), and the results were compared with those observed in dividing granulocytic precursors (DGP) and erythroblasts in a control group of 16 normal subjects. The parameters studied were: mitotic index (MI), labelling index (LI-3HTDR), MI/LI ratio and mitotic time (MT). The results showed that (1) LBC of AML do not proliferate more quickly than normal DGP, on the contrary, they replicate more slowly; (2) LBC obey some 'ecological laws' of normal hemopoiesis as a response to the control of the proliferative activity and release through the 'marrow-blood barrier'; (3) the difference between hyperleukocytemic and subleukemic AML is not related to the multiplicative activity of marrow LBC, but rather to other unknown biological factors; and (4) the kinetic behavior of erythroblastic population in AML is consistent, at least in some cases, with its 'leukemic origin'.
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One hundred and nine patients with Ph1-positive chronic myelocytic leukemia were cytogenetically studied with banding methods. Seventy-eight patients were studied in the chronic phase and 39 patients in the blastic phase. The standard translocation was present in 107 cases. Two patients showed complex translocations involving chromosomes No. 6, 9, 22, 11 and No. 9, 22, 11, respectively. Ph1-negative cells were detected in 8 cases (7%). Chromosome aberrations in addition to the Ph1 chromosome were observed in 6 cases (8%) during the chronic phase. The karyotypic findings during the blastic phase were similar to those reported in the past [trisomy 8, iso(17q), and a second Ph1]. The significance of Ph1-negative cells, the geographic heterogeneity of the chromosomal aberrations, the effect of chemotherapy on the appearance of new clones, and the importance of the materials and methods used for the comparison of cytogenetic patterns at different laboratories are discussed.
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