[Clonal chromosomal aberrations in patients with aplastic anemia at the disease onset and transformation].

AIM: To estimate detectability and characteristic features of chromosomal aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL AND METHODS: The trial covered 155 AA patients admitted to the Hematological Research Center in 1987-2002. Cytogenetic study by G-differential staining was performed in 58 patients with AA and 5 patients with AA transforming into myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and morphological specimens of the latter's bone marrow were studied retrospectively using fluorescent in situ hybridization (FISH) with DNA probes for detection of monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were detected in 4 out of 28 patients. Further examinations revealed no aberrations. Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of MDS/AL. In retrospective study of bone marrow specimens of patients with transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor neoplastic clone in the disease onset.

[Chromosomal aberrations in myelodysplastic syndrome].

AIM: To analyse incidence rate of chromosomal aberrations in myelodysplastic syndromes (MDS), specification of clinicomorphological features of some cytogenetic variants. MATERIAL AND METHODS: Chromosomal analysis by the method of G-differential staining of chromosomes was made in 209 patients with different variants of MDS. RESULTS; Clonal chromosomal aberrations occured in 60.8%. The following aberrations were found most frequently: deletion of the long arm of the chromosome 5 (del(5q)) - 34.6%, trisomy of chromosome 8 (14.1%), monosomy of chromosome 7 (13.4%), aberrations 3q21q26 (12.6%), aberrations of a long arm of X-chromosome (4.7%), the absence of Y-chromosome (3.1%). Complex aberrations of karyotype were found in 13.5% cases. Chromosomal aberrations determined not only clinical and morphological features but also the prognosis of the disease. CONCLUSION: Cytogenetic examination is an essential component of MDS patients examination. It allows more precise classification of MDS variant and prognostification of the disease course.

[Induced leukemias and their connection with radiation exposure]. / Indutsirovannye leikozy, ikh sviaz' s vozdeistviem radiatsii.

The cytogenetic study of bone marrow cells was performed in 40 patients with secondary leukemias which have arisen after application of cytostatic and/or radiotherapy for primary tumours (Hodgkin's disease, lymphomas, acute lymphoblastic leukemias, breast cancer and other solid tumours). The comparative analysis of results has shown, that the leukemias after irradiating or application of alkylating agents and irradiation, have the quite particular clinico-morphological and cytogenetic characteristics. In 70% of cases these diseases develops as smouldering leukemias with subsequent transformation in M-4, M-6, and rarely M-2 cytochemical variants. Primary cytogenetic events in 60% of researched karyotypes are the losses of long arms or whole chromosomes 5 and 7. In 20% of the researched cases normal karyotype was found, in the left 20%, the changes of a karyotype not including anomalies 5 and 7 chromosomes were detected. The obtained outcomes allow to consider the discharged complex of tags as reference for leukemias, induced by irradiating or chemical agents with similar mechanism of action (alkylating agents, benzene and its derivates). This complex of tags is typical for induced leukemias, and in a combination with definition of a level of stable aberrations in peripheral blood lymphocytes, can be utilised for abjection of radiation-induced leukemias from common mass of cases detected in regions, polluted by radionuclides. In this study in 60% of cases only specific for secondary leukemias chromosomal aberrations, including monosomy 5 and 7, rearrangements of 11q23 were found. On the base of the obtained data the differences in concepts of "secondary" and "induced" leukemias are considered.

[Molecular-cytogenetic monitoring of different regimens of treatment in patients with chronic myeloid leukemia]. / Molekuliarno-tsitogeneticheskii monitoring razlichnykh rezhimov terapii u bol'nykh khronicheskim mieloleikozom.

AIM: To conduct molecular-cytogenetic monitoring of bone marrow cells in different regimens of chronic myeloid leukemia (CML) treatment. MATERIAL AND METHODS: A total of 651 samples of bone marrow from 319 CML patients were studied. 229 patients received polychemotherapy and 90 patients--interferon-alpha. Primary examination and monitoring of the treatment efficacy were performed using G-differential chromosome staining. Fluorescent in situ hybridization (FISH) was made in 75% cases. RESULTS: Interferon therapy resulted in a significant increase in the number of complete and significant cytogenetic responses. With aggravation of the disease the above responses occurred less frequently while minor and no response are encountered more often. Treatment with interferon-alpha in combination with chemotherapy is much more effective than monotherapy with interferon. CONCLUSION: G-differential chromosome staining karyotypes metaphases and detects clonal chromosome restructuring. Molecular-cytogenetic methods study chromosome restructuring at DNA level. FISH detects chimeric gene bcr/abl in cases when Ph-chromosome is not detectable by standard cytogenetic methods.

[Cytogenetics of mantle cell lymphoma]. / Tsitogenetika limfomy iz kletok mantiinoi zony.

AIM: To determine the type and rate of secondary chromosomal aberrations and role in pathogenesis of mantle cell lymphoma (MCL). MATERIAL AND METHODS: Standard cytogenetic examination (SCE) and fluorescent in situ hybridization (FISH) with tests for 11q22/ATM, 13q14, 17p13/p53, 9p21/p16 and chromosome 12 centromere were made in 28 patients. RESULTS: Secondary chromosomal aberrations were detected in 22 patients. Chromosomal abnormalities occurring in more than 2 cases include deletions 6q15-q23 (53% cases); 11q22/ATM (50%); 9p21 (36%, in half the cases deletion 9p21 was biallele); 13q14 (32%); trisomy 3/3q, monosomy 20 and deletions/translocations 1q and 1p (27% and 20%) and deletion 17p13/p53 (18%). Trisomies 12/12q, 6 and 18/18q, monosomies 2 and 16, deletions/translocations 2p and 16p were found in 2 cases each. The FISH technique identified 9 chromosomal anomalies missed at SCE. Deletions 6q15-q23 were seen in patients with privalent lesions of lymph nodes. Deletions 11q, 13q14, 9p21 and 17p13 occur more frequently in transformation and the blastoid variant. Monosomy 20 was found only in patients with large cell transformations. This was the only cytogenetic defect characteristic for transformed cases, in contrast to denovoblastoid ones. Thus, deletions 6q, 11q23, 13q14 and 9p21 are typical for MCL. Deletions 9p21 and 17p13 are more characteristic for large cell variants of the tumor. Deletion 17p13 occurs at the terminal stage of the disease in rapidly growing tumor mass and resistance to chemotherapy. FISH technique is effective in detection of submicroscopic rearrangements especially small deletions. No significant differences were found between transformed and de novo blastoid cases. This shows that the blastoid variant is not a specific biological form, it is rather a less typical manifestation of the disease due to some preclinical cytogenetic disorders. CONCLUSION: Progression and transformation of MCL are related to mutation of proapoptotic genes and genes proteins of which are inhibitors of active complexes of D1 cycline. Specification of these mechanisms requires further investigations in patients with different clinicomorphological forms of the disease at various stages of the disease.

[T-cell tumors with aplastic syndromes]. / T-kletochnye opukholi, protekaiushchie s aplasticheskimi sindromami.

AIM: To detect and verify the existence of a specific form of T-cell tumor accompanied by isolated lesions of bone marrow and aplastic syndromes. MATERIAL AND METHODS: Four patients with aplastic syndromes were examined using clinical, histological, cytological, cytogenetic, and immunophenotypic methods. RESULTS: Four cases of T-cell tumors of bone marrow with clinical and morphological manifestations of aplastic syndrome and scanty proliferation activity in bone marrow alone were diagnosed. The proliferation activity in bone marrow was observed as formation of small clusters composed of small-size lymphoid cells with dense nucleus. Dynamic monitoring of two patients revealed a trend toward an increase in the lymphoproliferation base against the remaining clinical picture of aplastic syndrome. The T-cell immunophenotype characterized by disappearance of some markers or decrease in their density, was observed only in some blood and bone marrow lymphocytes. The most significant changes of immunophenotype were observed in one of the patients (CD2+CD3-CD4-CD5-CD7-CD8-CD16-CD56-CD45RO++). The same patient had pronounced cytogenetic changes (47XY+Y[8], 47, XY, del(1)(p10) [23], 46 XY [3]) and resistance to routine therapy, including cyclosporin. In one patient the process transformed into lymphosarcoma. CONCLUSION: The results obtained in four patients allow their clinicomorphological characteristics to be regarded as particular forms of T-cell tumors accompanied by bone marrow damage and aplastic syndrome.