Cytogenetic studies in 18 patients with secondary blood disorders.

Cytogenetic studies were carried out in 18 patients with secondary blood diseases; 15 patients had a history of prior malignancy, two had been professionally exposed to carcinogenic agents, and one patient had been treated with immunodepressors. The interval between initial therapy and secondary disease ranged from 13 to 123 months, with a mean of 57.8 months; the mean survival time from the diagnosis of secondary disease was 6 months. Cytogenetic abnormalities were present in 83% of cases, with a trend to hypodiploidy in 90%. The most often involved chromosomes were #5, #7, and 3p. A correlation between the cytogenetic abnormalities and etiologic factors has been analyzed; data from the present series and from the literature suggest a correlation between chromosome #7 and chemical agents, and chromosomes #11, #12, and #17 and physical agents.

Chromosome banding patterns in patients with chronic myelocytic leukemia.

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.

Karyotypic evolution in patients with myelodysplastic syndromes.

Serial cytogenetic studies were performed in 33 patients with myelodysplastic syndrome in order to establish the frequency of karyotypic evolution and to correlate the chromosome and clinical findings during the course of the disease. Fifteen of the 33 patients (45%) showed abnormalities in the first cytogenetic study and this percentage increased to 57% during the course of the disease. A stable karyotype (normal or abnormal) was found in 19 patients (58%), whereas the rest (42%) showed an unstable karyotype. Trisomy 8, monosomy 7, and del5q were the most frequent abnormalities, not only at presentation, but also during karyotypic evolution. Seven patients (23%) with a known evolution proceeded to leukemia; four of them had stable (22%) and three unstable (25%) karyotypes; however, 33% of patients with unstable karyotypes and only 5% with stable karyotypes died from complications of the disease. Our results suggest that karyotypic evolution is relatively frequent in these patients; this evolution could be related to a poor clinical prognosis, either evolving to leukemia or death.

Leukemic transformation in patients with the 5q- alteration: analysis of the behavior of the 5q- clones in preleukemic to leukemic phases.

Serial cytogenetic studies have been performed in four patients with myelodysplastic syndromes. In all four a 5q- alteration was present, but with a different pattern of presentation. One patient presented 5q- as the only alteration since diagnosis; two patients acquired this alteration during the course of the disease; and the fourth showed a 5q- plus other alterations since the first cytogenetic study. Likewise, three of the four patients showed a clone with trisomy 8 and without 5q-. According to these observations and others from the literature with similar cytogenetic behavior, we have analyzed the following points: 5q- as a primary event and as the only alteration, 5q- as a secondary event, 5q- plus other alterations, and presence of cytogenetically different clones. Analysis of these points suggests that the 5q- alteration can represent an early mutation conferring a slow capacity of expansion to the affected clones, with the possibility of cytogenetic evolution during the progression of the disease (about 30% of the patients). Likewise, the association of trisomy 8 clones with 5q- clones can be a nonrandom event.

[Thrombocytopoiesis and platelet kinetics]. / Trombocitopoyesis y cinética plaquetaria.

An up to date approach to different aspects of thrombocytopoiesis and platelet kinetics, in physiological conditions, han been done. The main parts of this review are: A historical revision of relation between megakaryocytes and platelets. An analysis of cellular basis of thrombocytopoiesis (morphological maturation gradient of megakaryocytes). Compartments of the stem cell population (multipotential stem cells and committed megakaryocytic stem cells). Functional compartments of polyploid megakaryocytes (multiplicative and madurative). Platelet formation from cytoplasmic projections of megakaryocytes in marrow sinusoids. Heterogeneity and life span of circulating platelets. Finally, the humoral regulation of platelets production is considered, mainly the two factors which appear to regulate thrombocytopoiesis, that is to say: colony stimulating factor and thrombopoietin.

Haemolytic anaemia to the alpha-interferon treatment: a proposed mechanism.

Auto-immune haemolytic anaemia (AIHA) has been found in a case of alpha-interferon treatment. Serum antibody and eluate were positive in the absence of the drug. Although the patient recovered after the treatment was stopped, DAGT remained positive for at least 8 months. The mechanism proposed to explain why this drug induced AIHA is similar to that proposed for alpha-methyl-dopa. Drugs could alter the red cell membrane and impair the immune system. Such changes have been observed with alpha-interferon and were related with increased autoimmunity.

[Clonal myelodysplasia: prognostic stratification and therapeutic possibilities]. / Mielodisplasias clonales: estratificación pronóstica y posibilidades terapéuticas.

Myelodysplastic syndromes represent an entire group of clonal panmyelopathies with very distinct evolutionary pathways. Their common denominator, however, is a self-maintained functional failure of the myeloid hemopoiesis which tends to evolve into severe non-lymphoid leukemia (SNLL) in 20-30% of the cases. First, the prognostic value of each the following is reviewed: the morphological classification F.A.B., the stratification system for "Bournemouth group", the abnormal placement of immature myeloid precursors (ALIP) in bone marrow, and cytogenetic changes. Second, the therapeutic potential for each of the following is assessed: vitamin and support treatments; suprarenal steroids; conventional androgens and danazol; agents of cellular differentiation (cytosine arabinoside in low doses, retinoid acids, vitamin D3, etc.). Finally, the role of aggressive chemotherapies (in succession or unrelated to marrow transplant) in the eradication of myelodysplastic clone or post-myelodysplasia SNLL is examined.

[Detection of translocation (15;17) using cytogenetic and molecular techniques. Comparative study in 15 patients with acute promyelocytic leukemia]. / Detección de la translocación (15; 17) con técnicas citogenéticas y moleculares. Estudio comparativo en 15 pacientes con leucemia aguda promielocítica.

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.

[Molecular analysis in 13 cases of chronic Philadelphia-positive myeloid leukemia]. / Análisis molecular en 13 casos de leucemia mieloide crónica Ph positivo.

Thirteen cases of Ph-positive CML have been studied from a cytogenetic and molecular point of view. All cases had Ph chromosome identified as t(9;22). Three of these cases were in blast crisis, and additional alterations to the Ph chromosome were found. The molecular study was made using the 3'bcr probe to analyze the ability to detect the translocation at the molecular level in bone marrow, peripheral blood, other tissues and in cases with mosaicism. Likewise we have evaluated the possibility to obtain molecular results from Carnoy-fixed samples which have been previously used in cytogenetic studies. In all cases we have detected rearrangement in the bcr region; this shows the interest and usefulness of this new methodology in the study of CML in different situations.

Kinetic behavior of 'pathological' myeloblasts and 'normal' erythroblasts in acute granulocytic leukemia. Analysis of in vitro studies in 20 patients.

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'.