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1.
Vestn Ross Akad Med Nauk ; (9): 28-32, 2009.
Article in Russian | MEDLINE | ID: mdl-19827640

ABSTRACT

Preliminary results of cytogenetic monitoring acute myeloid leukosis (AML) in children are presented. Repeated chromosomal analyses were accomplished in 23 patients that presented with cell clones showing various karyotype abnormalities prior to the onset of therapy. All the patients were treated following identical protocols. Complete hematological remission was achieved in 20 cases. The majority of patients did not have cells with chromosomal abnormalities changes after a 2-4 month follow up. Anomalous metaphases persisted in 6 patients although their occurrence decreased. Five of them poorly responded to therapy whereas simultaneous achievement of morphological and cytogenetic remission ensured more beneficial outcome of the treatment. Results of the study agree with recent reports of delayed reversion to normal karyotype under effect of AML therapy that as a rule predicts an unfavourable prognosis Repeated analysis during stable hematological remission did not reveal cells with karyotype abnormalities in bone marrow with the exception of a single patient who had marrow cells with chromosomal translocation (16:16) up to the 8th month of complete hematological remission. This patient remains under observation (duration of remission is now 15 months). It was shown that the relative amount of cells with abnormal karyotype in bone marrow frequently exceeds that of blast cells (usually before the onset of therapy and sometimes in the beginning of morphological remission). During stable remission, such an excess is an antecedent of relapse. It is concluded that cytogenetic analysis for monitoring AML extends the possibility of detecting leukemia cells.


Subject(s)
Bone Marrow Cells/pathology , Chromosome Aberrations , Leukemia, Myeloid, Acute/genetics , Adolescent , Child , Child, Preschool , Disease Progression , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Karyotyping , Leukemia, Myeloid, Acute/diagnosis , Male , Prognosis
2.
Vestn Ross Akad Med Nauk ; (6): 9-16, 2009.
Article in Russian | MEDLINE | ID: mdl-19642542

ABSTRACT

Prognostic significance of additional karyotype abnormalities was studied in 73 children with t(8,21) acute myeloid leukemia (AML). Additional chromosomal aberrations were documented in 61 cases (83.6%). The loss of sex chromosomes and/or deletion of the long arm of chromosome 9 (9q-) were predominant abnormalities, in agreement with the literature data. Other additional abnormalities detected in 14 cases were tentatively designated as "atypical". Comparison of pretreatment cytogenetic data and those obtained during relapses revealed the previously unknown rise in the frequency of atypical abnormalities in AML relapses (to 63.6% vs 19.2% at the first presentation, p < 0.005). It is supposed that atypical additional abnormalities reflect relatively late stages of leukemia, and their presence before therapy predicts poor prognosis. In fact, general, relapse-free, and uneventful survival rates in patients with atypical abnormalities were significantly lower that in the remaining patients with t(8;21) AML. Poor survival was associated not only with early relapses but also with high mortality from fatal infections soon after onset of treatment. The incidence of fatal infections in this group was significantly higher than in patients without atypical abnormalities (p = 0.027). Atypical additional abnormalities are rather variable and each variant should to be specifically characterized to estimate its prognostic significance. Our results need to be verified in a larger-scale multicentre study.


Subject(s)
Chromosomes, Human, Pair 21/genetics , Chromosomes, Human, Pair 8/genetics , Leukemia, Myeloid, Acute/genetics , Translocation, Genetic , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Karyotyping , Leukemia, Myeloid, Acute/mortality , Male , Prognosis , Russia/epidemiology , Survival Rate/trends
3.
Vestn Ross Akad Med Nauk ; (5): 3-7, 2008.
Article in Russian | MEDLINE | ID: mdl-18589906

ABSTRACT

A majority of the data on the prognostic significance of distinct chromosome changes and combinations of them in pediatric acute myeloid leukemia (AML) has been derived from adult studies, with not numerous published data in pediatric patients. One of points needed to be clarified is prognostic significance of complex karyotype (at least 3 unrelated abnormalities). We investigated characteristic features of complex karyotype in newly diagnosed pediatric AML de novo. Cell clones with complex karyotype were found in 35 of 254 (13.8%) patients at the age from 0 to 15 years studied prior to therapy. The group was divided into 2 subgroups depending on presence of favorable chromosome abnormalities, i.e. (see symbols)(8;21), t(15;17) and inv(16). The abnormalities were absent in 20 cases (1st subgroup), in 15 remaining patients they were identified (2nd subgroup). In 2nd subgroup karyotypes were not so considerably changed and no adverse risk markers were detected as distinct from 1st subgroup. New data were obtained for complex karyotype differences of adult and pediatric AML. In the great majority (76%) of complex karyotypes in our adult patients chromosome abnormalities associated with adverse risk were found but in pediatric patients their frequency was significantly less (30%). The highest rate of complex karyotype we observed in children at the age from 0 to 3 years. Similar data were not published earlier. Complex karyotype is considered to be characteristic of older AML patients and in the majority of the patients the karyotype contains markers of adverse risk. Possibly, worse outcome in older AML patients is connected with the markers but not with multiple chromosome changes. New data of frequency and the peculiarities of complex karyotype in pediatric AML are important for understanding of AML pathogenesis and for development a more effective AML treatment.


Subject(s)
Bone Marrow Cells/pathology , Chromosome Aberrations , Leukemia, Myeloid, Acute/genetics , Adolescent , Child , Child, Preschool , Clone Cells/pathology , Diagnosis, Differential , Female , Humans , Infant , Infant, Newborn , Karyotyping , Leukemia, Myeloid, Acute/pathology , Male , Prognosis
4.
Ter Arkh ; 79(7): 26-30, 2007.
Article in Russian | MEDLINE | ID: mdl-17802786

ABSTRACT

AIM: To analyse the results of treatment of children and adolescents with acute promyelocytic leukemia (APL) including polychemotherapy and ATRA (protocols APL 93, 98 and 2003). MATERIAL AND METHODS: The course of the disease, modification of the treatment protocols with reduction of anthracyclines and ATRA doses, results of molecular monitoring of PML/RARalpha transcript have been analysed for 107 APL patients. RESULTS: For prognosis of the disease important are initial characteristics of the patient and the time of the tumor regress assessed by molecular methods--establishment of molecular remission and molecular recurrence. CONCLUSIONS: In APL it is necessary to conduct molecular monitoring especially in patients at high risk and with poor prognosis in a decrease of treatment intensity for toxicity relief. Detection of molecular recurrence is indication for treatment. To raise efficacy of APL recurrence therapy it is necessary to design a special updated protocol.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Receptors, Retinoic Acid/genetics , Transcription, Genetic/drug effects , Adolescent , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Child , Child, Preschool , Female , Humans , Leukemia, Promyelocytic, Acute/mortality , Male , RNA, Messenger/analysis , Retinoic Acid Receptor alpha , Treatment Outcome
6.
Arkh Patol ; 60(4): 61-71, 1998.
Article in Russian | MEDLINE | ID: mdl-9791701

ABSTRACT

Diagnostic criteria of T-cell lymphoma and Hodgkin's disease are presented which are the basis of the European-American classification schema (REAL). Brief morphological, immunophenotypical, genetic and clinic characteristics of every tumor type (subtypes variants) are given. The comparison of this REAL section with the Kiel's classification is made with some critical notes concerning, in particular, the Hodgkin's disease classification.


Subject(s)
Hodgkin Disease/classification , Lymphoma, T-Cell/classification , Hodgkin Disease/genetics , Hodgkin Disease/pathology , Hodgkin Disease/physiopathology , Humans , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/physiopathology
7.
Genetika ; 34(8): 1049-55, 1998 Aug.
Article in Russian | MEDLINE | ID: mdl-9777351

ABSTRACT

Most colorectal tumors are characterized, among other genetic alterations, by allele loss of the genes located on the short arm of chromosome 17 (17p13.1), including the p53 suppressor gene. In ovarian and mammary-gland tumors, deletions of another candidate tumor-suppressor gene, located in the 17p13.3 chromosome region, were observed. We analyzed allele losses in the loci of the short arm of chromosome 17 (YNZ22, MCT35.1, and the p53 gene) in colorectal-cancer patients from the former Soviet Union. Tumors with cytogenetic alterations in 17p and/or with a detected loss of heterozygosity at the YNZ22 (D17S30) locus were examined for allele losses in the p53 gene using two polymorphic sites. Different methods revealed alterations on 17p in 24 (48%) out of 50 patients with colorectal carcinomas. In all tumors with an allele loss of the YNZ22 marker (15 out of 44 informative cases), which was detected by means of PCR, allele loss of the p53 gene was found (12 out of 15 informative cases). In 5 out of 13 tumors with cytogenetic alterations in 17p, allele loss of the p53 gene was found, with the YNZ22 marker being unaffected. In one of these tumors, the i(17q) marker was found, and in the remaining four tumors, 17p translocations were detected. In 4 out of 5 tumors with translocations affecting 17p, the t(17;20)(q21;p12) translocation was detected. The informativeness of the screening for 17p translocations, using PCR for the YNZ22 locus, and the reasons for discrepancy between the data of PCR and cytogenetic analyses are discussed.


Subject(s)
Chromosome Aberrations/genetics , Chromosomes, Human, Pair 17 , Colorectal Neoplasms/genetics , Genes, p53 , Alleles , Chromosome Disorders , Gene Deletion , Genetic Markers , Humans , Loss of Heterozygosity , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Translocation, Genetic
9.
Genetika ; 33(9): 1297-302, 1997 Sep.
Article in Russian | MEDLINE | ID: mdl-9445823

ABSTRACT

Karyotypic structural aberrations in tumor cells and chromosome constitutive fragile sites (cFSs) in peripheral blood lymphocytes were studied in ten patients with colorectal adenocarcinoma Most chromosome breakpoints (38 out of 40, i.e., 95.0%) were shown to be located within cFSs in tumor cells. Expression of 24 out of 137 cFSs in patients was higher than that in healthy donors. Four of these cFSs (6q26, 7q36, 16q23, and 17q21), were involved in the formation of nonrandom tumor cell chromosome markers most characteristic of colorectal neoplasms. The frequency of damages induced within these sites was analyzed in each patient. Expression of 7q36, 16q23, and 17q21 was increased in blood cells of patients carrying specific chromosome rearrangements with the breakpoints within these sites. The association between nonrandom chromosome aberrations in tumor cells and cFSs in normal cells is discussed.


Subject(s)
Adenocarcinoma/genetics , Chromosome Aberrations , Chromosome Fragility , Colorectal Neoplasms/genetics , Adult , Aged , Case-Control Studies , Chromosome Fragile Sites , Female , Humans , Karyotyping , Male , Middle Aged
10.
Arkh Patol ; 58(4): 28-32, 1996.
Article in Russian | MEDLINE | ID: mdl-8967859

ABSTRACT

A case of metachronous cancer of gastrointestinal tract is reported. Three poorly differentiated malignant epithelial tumours developed in a 27-year-old patient within three years. They located in the stomach, small and large intestine. Light-microscopically, the tumours were formed mainly of non-differentiated rounded cells with occasional signet ring cells. At electron microscopic examination the presence of mucin granules was confirmed. Moreover, a variable amount of electron-dense endocrine-like granules was found in tumour cells. According to some publications, endocrine differentiation of gastrointestinal cancers is considered to be a poor prognostic feature, hence electron microscopy or special staining when possible can be important in the evaluation of prognosis.


Subject(s)
APUD Cells/pathology , Carcinoma/pathology , Gastrointestinal Neoplasms/pathology , Neoplasms, Second Primary/pathology , Adult , Carcinoma/genetics , Cell Differentiation/physiology , Gastrointestinal Neoplasms/genetics , Humans , Karyotyping , Male , Microscopy, Electron , Mucins/ultrastructure , Neoplasms, Second Primary/genetics , Prognosis
11.
Arkh Patol ; 58(4): 41-3, 1996.
Article in Russian | MEDLINE | ID: mdl-8967864

ABSTRACT

The authors' material (33 tumours) and that from foreign literature (18 to 100 tumours from every country) was used. The following chromosome aberrations were compared: the deletion of a part of chromosome 1 short arm, deletion of chromosome 5 and a part of its long arm, additional chromosomes 7, complete or partial deletion of chromosome 17 short arm, deletion of chromosome 18 and appearance of additional chromosomes 20. Clear-cut differences were revealed between the following three groups of regions: 1) countries of the Eastern and Western Europe (Russia, France, Germany); 2) Northern Europe countries (Denmark, SWeden); 3) USA and China. Geographical differences in chromosome anomalies in hemoblastosis were found in 1970s, the difference in colon carcinoma are presented for the first time. The experimental results suggest that non-homogeneous distribution of the karyotype alterations typical for certain morphological types of malignant tumours are due to different environmental influences.


Subject(s)
Chromosome Aberrations/genetics , Colorectal Neoplasms/genetics , China/epidemiology , Chromosome Disorders , Colorectal Neoplasms/epidemiology , France/epidemiology , Germany/epidemiology , Humans , Karyotyping , Scandinavian and Nordic Countries/epidemiology , United States/epidemiology
12.
Klin Lab Diagn ; (6): 70-2, 1995.
Article in Russian | MEDLINE | ID: mdl-8589969

ABSTRACT

Examinations of 174 children and 188 adult patients with acute nonlymphoblastic leukemia (ANLL) demonstrated a similar structure of distribution of ANLL FAB-variants in children and adults, although the incidence of M0 and M4 blasts was somewhat higher in infants aged under 2. In patients under 15 and over 60 peroxidase activity in myeloblasts was reliably lower than in the rest patients. HLA-Dr, Thy-1, CD11a, T-CD19, Gly-A, and Eb antigens were equally incident in the cells of children and adults. The expression of CD11b, CD38, and CD10 antigens on the blasts was higher in children than in adults. An abnormal blast karyotype was detected in 81.8% children and 73.7% adults. Translocation (8;21) was observed in patients with the M2 variant, as a rule (82%), and reliably more frequently in children; t(9;22) and t(11q23) occurred in children somewhat more frequently than in adults. A group of children with primary ANLL (n = 3) was distinguished for the first time, in whose cell karyotype a deletion of chromosome 5 was found. The findings indicate that the biological characteristics of blast cells differ in children and adults. Evidently, the level of hemopoiesis involvement in ANLL is earlier in infants under 2 and subjects over 60 than in the rest patients.


Subject(s)
Leukemia, Myeloid, Acute/diagnosis , Adolescent , Adult , Biomarkers/blood , Child , Child, Preschool , Chromosome Aberrations , Clinical Enzyme Tests , Humans , Immunophenotyping , Infant , Middle Aged , Peroxidase/blood
13.
Ter Arkh ; 67(7): 12-6, 1995.
Article in Russian | MEDLINE | ID: mdl-7482296

ABSTRACT

Megakaryocytic dysplasia, platelet and megakaryocytic counts were measured in 87 ANLL patients. High megakaryocytic levels were registered in 16.1%, normal in 17.2%, low or negligible in the rest of the examinees. Half of the patients had dysplasia. Thrombocytopenia present in 93% of cases attested to ineffective proliferation of megakaryocytes. Increased number of megakaryocytes with signs of dysplasia occurred more commonly in M0- and M4- variants of ANLL universally in anomalies of chromosome 3 long arm with involvement of q21 and/or q26 segments and occasionally in combination with other chromosome disorders. Megakaryocytosis developed less frequently in patients with ANLL variant M2 with t (8;21) and did not correlate with granulocyte and erythroid cell dysplasia. Pronounced megakaryocytosis in combination with thrombocytosis emerged in 4 patients: 2 of them had typical anomalies of chromosome 3--inv3(q21q26) and dup (3q21q26), 1 had monosomy 7 and 1 normal karyotype. Potential mechanisms responsible for dysplasia of megakaryocytes in ANLL are considered.


Subject(s)
Leukemia, Myeloid, Acute/pathology , Megakaryocytes/pathology , Adolescent , Adult , Aged , Bone Marrow/metabolism , Bone Marrow/pathology , Cell Count/methods , Chromosome Aberrations , Chromosomes, Human, Pair 3 , Female , Histocytochemistry , Humans , Immunophenotyping , Karyotyping , Leukemia, Myeloid, Acute/genetics , Male , Megakaryocytes/metabolism , Middle Aged
14.
Ter Arkh ; 66(7): 7-10, 1994.
Article in Russian | MEDLINE | ID: mdl-7985136

ABSTRACT

The paper presents the results of the retrospective study of blast cells from 377 patients with acute nonlymphoblastic leukemia (ANLL). Morphocytochemical, immunological, cytogenetic assessments and cloning in semisolid agar were employed. The authors specify blast characteristics with reference to ANLL variants according to the FAB classification, define diagnostic criteria for poorly differentiated myeloblastic (MO), erythroblastic (M6) and megakaryoblastic (M7) leukemia, hybrid variants.


Subject(s)
Leukemia, Myeloid, Acute/diagnosis , Adult , Antibodies, Monoclonal , Bone Marrow Examination , Histocytochemistry , Humans , Immunophenotyping , Karyotyping , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/pathology , Moscow , Preleukemia/diagnosis , Retrospective Studies
15.
Gematol Transfuziol ; 39(1): 3-6, 1994.
Article in Russian | MEDLINE | ID: mdl-8188030

ABSTRACT

Twenty-five patients with acute lymphoblastic leukemia [15 adults and 10 children] received standard treatment in which regular L-asparaginase was replaced for L-asparaginase of prolonged action [PEG-asparaginase]. The drug was administered once in two weeks in a dose 2500 IU/m2 for remission induction and consolidation or as a component of maintenance therapy. It was found that the response to primary PEG-asparaginase treatment or its use in the disease relapses produced the same response as regular L-asparaginase, being superior in convenience and feasibility of outpatient use. Side effects in the form of hypoproteinemia, hepatic toxicity and toxic pancreatitis [in children, 9 and 1 adults, respectively] were moderate and disappeared after 10-20-day discontinuation of the drug.


Subject(s)
Asparaginase/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Delayed-Action Preparations , Female , Humans , Male , Middle Aged
16.
Ter Arkh ; 63(7): 109-11, 1991.
Article in Russian | MEDLINE | ID: mdl-1788786

ABSTRACT

Results of the treatment of 30 adult patients with acute lymphoblastic leukemia are analyzed. Before the treatment was commenced, the patients were distributed into groups with a favourable, intermediate and unfavourable prognosis depending on the signs previously defined by the authors. In the phase of induction and consolidation of a remission, the treatment intensity in these groups varied. The rate of complete remissions (CR) reached 70% in the whole group; provided Ph-positive ALLs were excluded from the analysis, it was 75%, the median duration of the CR amounted to 21 months, the projected 4-year relapse-free survival was 41%. In the group of historic control (31 patients treated in accordance with the unified program), these indicators were 58 and 69%, 18 months, and 21%, respectively. All the differences appeared statistically insignificant. In spite of the total treatment intensification, the rate of lethal outcomes did not rise during remission induction.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/administration & dosage , Female , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Prednisolone/administration & dosage , Prognosis , Remission Induction , Vincristine/administration & dosage
17.
Ter Arkh ; 59(6): 27-31, 1987.
Article in Russian | MEDLINE | ID: mdl-3477030

ABSTRACT

The results of programmed therapy of acute lymphoblastic leukemia (ALL) in 31 adult patients were analyzed. Ph-positive ALL were marked in 5 patients. Low hemosuppressive induction, heavy consolidation and multidrug maintenance therapy was used. Complete remissions were obtained in 18 patients, their median time was 18 months (from 2 to 46 months). The patients were divided into groups with a good, intermediate and poor prognosis on the basis of an immunological ALL variant, the presence or absence of basal hyperleucocytosis and Ph-chromosome. Data on adequate therapy for each group were presented.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphoid/drug therapy , Adolescent , Adult , Aged , Female , Humans , Leukemia, Lymphoid/classification , Male , Middle Aged , Prognosis , Remission Induction
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