[Chromosomal translocation t(8,21) in acute myeloid leukemia of children: prognostic value of additional karyotype abnormalities].

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.

[Complex karyotype abnormalities in pediatric acute myeloid leukemia].

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.

Quantitative estimation of chromosome aberration frequency in cancer patients induced by endogenous and exogenous factors.

In patients with skin melanoma and colon cancer, cell distribution by the number of chromosome aberrations cannot be described by Poisson distribution, but corresponds to a bipopulation model combining the Poisson and geometric distributions. In contrast to the control, in patients with malignant tumors, cells with geometric distribution possess the majority of chromosomal aberrations.

Increased karyotype precision using fluorescence in situ hybridization and spectral karyotyping in patients with myeloid malignancies.

We studied seven patients with various malignant hematologic disorders using fluorescence in situ hybridization (FISH) and one of these patients with spectral karyotyping (SKY). With appropriate probes, the t(8;21) and inv(16) were confirmed in two patients and the karyotypic precision was increased in five others using FISH and SKY. Two of three patients with 12p rearrangements had a deletion of one TEL allele. Thus, these newer techniques are an important adjunct to accurate chromosome analysis in malignancy.

[Karyotypic anomalies and chromosomal sites of increased fragility in colorectal cancer]. / Anomalii kariotipa i saity povyshennoi lomskiti khromosom pri kolorektal'nykh rakakh.

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.

[Metachronous cancer of the gastro-intestinal tract with signs of endocrine-cell differentiation]. / Metakhronnyi rak zheludochno-kishechnogo trakta s priznakami éndokrinnokletochnoi differentsirovki.

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.

Enhanced expression of 1p32 and 1p22 fragile sites in lymphocytes in cutaneous malignant melanomas.

Frequency and distribution of 5-fluorodeoxyuridine (5-FdU) plus caffeine-induced fragile sites on chromosomes of peripheral blood lymphocytes (PBL) from 10 patients with cutaneous melanoma were studied in comparison with 10 PBL samples from normal donors of corresponding sex and age. The total number of breaks showed a significant difference among individuals in both groups, however, the average frequencies of 5-FdU plus caffeine-induced, as well as spontaneous damages in PBL from melanoma patients, were higher than those from healthy volunteers. The analysis of the breakpoint distribution showed a statistically significant increase in the expression of several fragile sites. The highest enhancement was observed at 1p32 and 1p22 sites (p less than 0.001). Earlier, the increase in the expression of 1p32 fragile sites was reported for neuroblastoma patients. We believe that enhanced expression of fragile sites in 1p may play a yet-unknown pathogenetic role in the development of some neuroectodermal tumors.

[Study of the decomposition of alkylating mutagens of the ethyleneimine series in human lymphocyte cultures]. / Issledovanie razlozheniia alkiliruiushchikh mutagenov étileniminovogo riada v kul'ture limfotsitov cheloveka

A simple method of determination (with a high reproducibility) of concentrations of the alkylating compound in the culture medium is described. Thiophosphamide failed to decompose in the course of 24 hours either in the culture mixture or in the human lymphocyte culture. As to phosphamide, dipine and fotrin, these drugs disintegrated significantly in the culture during 24 hours, but not in the course of the first 6 hours.

[Relationship between the cytogenetic effect of different concentrations of thiophosphamide and phosphemide and the duration of their contact with human lymphocytes]. / Zavisimost' tsitogeneticheskogo deistviia razlichnykh kontsentratsii tiofosfamida i fosfemida ot vremeni kontakta ikh s limfotsitami cheloveka

The effect of thiophosphamide at conccentrations of 10, 20 and 30 mcg/ml and phosphamide at concentrations of 35 and 50 mck/ml on human lymphocyte chromosomes at different time of the contact was investigated. The experiments were carried out at GO phase (before adding FGA) at 37 degrees C from 10 to 240 minutes. The fixation was made within 58th hour. A mathematical model, satisfactory describing experimental data on the reaction of mutagen-chromosome interaction during the time of exposition, is suggested. According to this model, the following equation are obtained: rho = (1 - e-(alpha+Kt))2; chi = (see article), where rho is a portion of aberrant cells, chi is the average number of breaks per cell, t is the time of exposition of mutagens with cells, alpha and K are coefficients. Breaks induced by thiophosphamide and phosphamide are distributed among cells according to geometrical parameter under any experimental conditions. The portion of chromatid breaks did not change at any exposition time for both mutagens and remained on the level of 76,53%. The proportion of symmetric and asymmetric exchanges under different experimental conditions did not differe from 1 : 1. The prabability of the formation of complete exchanges in the case of the action of thiophosphamide was higher than in the case of phesphamide.

[The relationship between the cytogenetic action of thiophosphamide and the duration of human cell treatment]. / Zavisimost' tsitogeneticheskogo deistviia tiofosfamida ot dlitel'nosti obrabotki kletok cheloveka

The subject of the present investigation is the expositional curves of the effect of thiophosphamide (as a drug and chemically pure compound) on chromosomes of human leucocytes at concentrations of 20 and 30 mcg/ml. Thiophosphamide was shown to retain its mutagenic activity during the 8 hrs incubation in the medium under the temperature of 37 degrees C. The percent of aberrant cells and the number of chomosome breaks per 100 cells appeared to show non-linear dependence on the exposition at different concentrations of thiophosphamide. The percent of aberrant cells as a function of the exposition of the mutagen can be satisfactorily described by the equation rho=-a exp [-Kt], where rho is a portion of aberrant cells, a and K are the coefficients, t is the time of the exposition of cells to the mutagen. But this equation results in a negative value of a number of aberrant cells in the control. No satisfactory description of the change in the number of chromosome breaks was found. The portion of chromatid breaks did not change under any exposition and remained at the level of 80%. The proportion of symmetric and asymmetric, complete and incomplete exchanges under different expositions with thiophosphamide did not change and did not differ from 1:1. Isoeffective points for different expositions to and concentrations of thiophosphamide were not obtained, this suggests a non-additive relationship between concentrations and expositions to thiophosphamide.