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Biomedical subjects

R Kusec

Publications and source records attributed to R Kusec.

26 records · Page 2Linked to original sources
PubMed1994

Molecular mechanism of the t(14;18)--a model for lymphoid-specific chromosomal translocations.

The chromosomal translocation t(14;18) occurs during early B-cell development and juxtaposes the immunoglobulin heavy chain locus (IgH) with the bcl-2 oncogene. Several factors contribute to the translocation mechanism: (1) The rearrangement of the chromosome 14 DH and JH translocation partners has typical features of V(D)J-recombinase-mediated joining with N-segment addition. (2) The bcl-2 major (mbr) and minor (mcr) breakpoint regions as well as their IgH reciprocal counterparts contain recombinatorial sequences related to chi or the minisatellite-core which bind at least one common DNA-binding protein (bp45). Similar elements are found at the breakpoints of other lymphoid-specific translocations like the t(11;14), t(2;8) or the t(4;11). (3) Structural analysis of the bcl-2 mbr indicates that this region may adopt alternative DNA-configurations which can promote recombination and is cleaved by an endogenous nuclease present in early B-cells. The present data suggest that V(D)J-recombinase as well as chi/minisatellite-core mediated recombination contribute to the mechanism and make the t(14;18) a model system for lymphoid-specific reciprocal translocations.

Base Sequence↗
PubMed1994

AML1/ETO fusion mRNA can be detected in remission blood samples of all patients with t(8;21) acute myeloid leukemia after chemotherapy or autologous bone marrow transplantation.

The chromosomal translocation t(8;21)(q22;q22) in acute myeloid leukemia (AML) can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the chimeric AML1/ETO transcript. We have evaluated the clinical relevance of this method for monitoring and detection of minimal residual disease (MRD) in seven patients who reached a complete hematological remission (CHR) after chemotherapy or autologous bone marrow transplantation (ABMT). Peripheral blood (PB) samples of five patients in first continuous complete remission (CCR) were still PCR-positive at a frequency of 1 in 10(5) cells after 7, 8, 8, 10 or 66 months. Chemotherapy led to a reduction from first- to second-step PCR-positivity in three serially monitored patients. AML1/ETO mRNA was also detected in the PB of two patients in CCR, 10 or 12 months after ABMT. PB and bone marrow (BM) showed identical results in all samples tested simultaneously. AML1/ETO fusion transcripts were neither found in the PB and BM of a healthy individual, nor in the PB of a patient after allogeneic BMT for cytogenetically proven t(8;21)-leukemia. Our results indicate the presence of cells carrying the AML1/ETO rearrangement in the PB and BM of all patients in CHR after chemotherapy or ABMT for t(8;21)-positive AML. While this finding raises interesting questions about the biology of acute leukemia, it limits the value of the AML/ETO RT-PCR for the prediction of impending relapse.

Adult↗
PubMed1993

Myeloid hemopoietic growth factors. Review article.

The article is a critical review of recent publications on myeloid hemopoietic growth factors. They are glycoproteins that regulate the proliferation and differentiation of hemopoietic progenitor cells and the function of mature blood cells. They are also named colony stimulating factors after the experimental technique that led to their discovery. Myeloid growth factors are: granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF) and interleukin-3. Studies of hemopoietic growth factors in the past years have revealed many potential beneficial effects, but some limitations as well. They have been proved effective, above all, in neutropenic conditions of different origin. A large number of clinical trials have shown their beneficial effect in myelosuppressive conditions after cytotoxic chemotherapy, in post-transplant period in bone marrow transplantation procedures and in neutropenic conditions as part of other clinical entities. Although a number of studies that should determine their clinical role more clearly is still underway, it seems certain that myeloid hemopoietic growth factors already have an important role in modern pharmacotherapy.

Animals↗
PubMed1991

The roles of age and sex in the prognosis of chronic leukaemias. A study of 373 cases.

The roles of age and sex and their relationship to other prognostic factors were studied in 117 chronic myeloid leukaemia (CML) and in 256 chronic lymphocytic leukaemia (CLL) patients. Survival in CML was not related either to age at diagnosis or to sex. In contrast, the CLL patients classified into four age strata (less than 50, 50-59, 60-69, greater than 70 years) had an expected median survival (EMS) of 142, 101, 85 and 33 months respectively (chi 2 for heterogeneity = 35.59, P less than 0.0005; chi 2 for trend = 25.09, P less than 0.0005). Prognostic power was independent of sex, Rai stages, total tumour mass score (TTM), TTM distribution pattern, anaemia, thrombocytopenia, serum immunoglobulins and response to therapy. The relative survival rate (the ratio of patient's EMS and EMS in age- and sex-matched general population) was 0.40 in CLL patients and 0.13 in CML patients. Relative survival was more reduced in older CLL patients than in younger ones (0.37 vs 0.47, respectively), whereas relative survival was less reduced in older CML patients than in younger ones (0.18 vs 0.12, respectively). The results show that the age is a significant independent prognostic factor in CLL but not in CML. The difference in the effects of age on prognosis in CLL and CML most probably reflects the fundamental differences in their respective pathogeneses.

Age Factors↗
PubMedDate not supplied

Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML.

The chromosomal translocation t(8;21) (q22;q22) is often associated with acute myeloid leukemia with maturation (AML-M2) and can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the AML1/ETO fusion mRNA. We investigated the prevalence of t(8;21) and AML1/ETO in 204 unselected patients with AML and compared the results of cytogenetic analysis with these of RT-PCR. Fifteen of 204 AML patients (7.4%) showed a t(8;21) in karyotype analysis. In 17 of 204 patients (8.3%) AML1/ETO was detected by RT-PCR. All patients who had a t(8;21) in conventional karyotyping also showed the gene rearrangement in molecular analysis, including one patient with a three-way translocation t(5;8;21). AML1/ETO was also detected in two AML patients lacking the t(8;21) cytogenetically. One had a normal diploid karyotype bone marrow (BM) at diagnosis; she has now been in CCR for 12 months. The second patient showed a complex chromosomal anomaly involving chromosome 21, but without a typical 8;21 translocation (BM in relapse). He died in relapse after an overall survival of 60 months. These data indicate that the results of karyotyping and RT-PCR are not completely identical, and molecular biology identifies approximately an additional 5-10% of AML1/ETO positive cases. The clinical relevance of our findings will have to be evaluated with larger patient numbers.

Acute Disease↗