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At least 631 records · Page 35Linked to original sources
PubMed2002

Fluorescence in situ hybridization improves cytogenetic results in the analysis of hepatoblastoma.

Hepatoblastoma (HB) is the most frequent malignant liver tumor in children. Cytogenetic data indicate the presence of recurring trisomies of the chromosomes 2, 8, and 20, but more work is needed to clarify their incidence and prognostic significance. Cytogenetic analysis is limited by the requirement of suitable cells in metaphase. A different method that increases analysis sensitivity is fluorescence in situ hybridization (FISH). We studied 20 cases of hepatoblastoma; FISH analysis obtained results in 10 cases of HB with no informative karyotype. In 5 of 10 of these cases at least one trisomic clone was detected, which always coexisted with a population of diploid cells. These results confirm that trisomy 20 and/or 2 and 8 coexisting with diploid cells is a frequent finding in hepatoblastoma and provide further support to the clonal evolution theory: indeed, trisomy 20 was the most frequently detected abnormality, followed by trisomy of chromosomes 2 and 8. In view of the high incidence of recurrent trisomies, FISH analysis should be recommended in all the cases of HB with no informative karyotype.

Adult↗
PubMed2002

Compilation of published comparative genomic hybridization studies.

The power of comparative genomic hybridization (CGH) has been clearly proven since the first paper appeared in 1992 as a tool to characterize chromosomal imbalances in neoplasias. This review summarizes the chromosomal imbalances detected by CGH in solid tumors and in hemopathies. In May of 2001, we took a census of 430 articles providing information on 11,984 cases of human solid tumors or hematologic malignancies. Comparative generic hybridization has detected a number of recurrent regions of amplification or deletion that allows for identification of new chromosomal loci (oncogenes, tumor suppressor genes, or other genes) involved in the development, progression, and clonal evolution of tumors. When CGH data from different studies are combined, a pattern of nonrandom genetic aberrations appears. As expected, some of these gains and losses are common to different types of pathologies, while others are more tumor-specific.

Chromosome Aberrations↗
PubMed2002

Spontaneous clinical and cytogenetic remission of aplastic anemia in a patient with del(13q).

We describe the case of a 64-year-old Japanese man with pancytopenia. Bone marrow biopsy findings were consistent with aplastic anemia. The patient was treated by transfusions without immunosuppressive therapy. Chromosome analysis of bone marrow cells at 6 months after onset showed a 46,XY,del(13) (q14q22) karyotype. The pancytopenia resolved gradually over the next 5 years; chromosome analysis of bone marrow cells at that time yielded normal findings. To our knowledge, this is the first report of spontaneous hematologic and cytogenetic remission of aplastic anemia. These findings suggest that the abnormal clone with deletion of the long arm of chromosome 13 was not sufficient for clonal evolution in aplastic anemia in this case.

Anemia, Aplastic↗
PubMed2002

SKY detection of chromosome rearrangements in two cases of tMDS with a complex karyotype.

In this study, we used spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) as complementary techniques for the analysis of two therapy-related secondary myelodysplastic syndrome (t-MDS) cases with complex karyotypes, previously analyzed by G-banding. Different types of SKY's cytogenetic contributions include confirmation of G-banding results, identification of partially characterized rearrangements, identification of marker chromosomes unidentified by G-banding, and detection of cryptic reciprocal translocations. In particular, the ability of SKY to clarify a number of markers led to the comprehension of clonal evolution. The common aberration found in these two t-MDS cases was the fragility of chromosome 5 and monosomy of chromosome 18. We clearly present that the use of SKY combined with conventional G-banding analysis and FISH has assisted in the identification of important chromosomal events that may play a key role in the development of t-MDS.

Aged↗
PubMed2002

Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation.

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.

Adult↗
PubMed2003

Multiple myeloma with monosomy 13 developed in trisomy 13 acute myelocytic leukemia: numerical chromosome abnormality during chromosomal segregation process.

We report here an acute myelocytic leukemia (AML-M2) patient with trisomy 13 as the sole cytogenetic anomaly, who had relapse of AML with a normal karyotype and developed multiple myeloma. Fluorescence in situ hybridization analysis using the RB gene probe revealed the plasma cells of multiple myeloma (MM) to have monosomy 13 anomaly, whereas relapsed blast cells of AML carried disomy of chromosome 13. To our knowledge, this is the first case showing clonal evolution of trisomy 13 AML and monosomy 13 MM, which might be derived from the leukemic clone at relapse.

Chromosome Aberrations↗
PubMed2003

Translocation (12;21) followed by insertion of chromosome 3 material in the derivative chromosome 12 in a case of childhood acute lymphoblastic leukemia.

We report a 2-year-old boy with B-cell acute lymphoblastic leukemia. Cytogenetic studies at diagnosis with R-banding showed a 46,XY,ins(12;3)(p13;q?21q?22)/46,XY karyotype. Fluorescence in situ hybridization with TEL/AML1 probes and chromosome paints revealed complex rearrangements. The TEL/AML1 fusion gene was located on the derivative chromosome 21 but a segment of the long arm of a chromosome 3 was inserted between the proximal part of the short arm of the derivative chromosome 12 and the reciprocal part of the AML1 gene. This is consistent with an insertion of chromosome 3 into chromosome 12 after the t(12;21) took place, therefore indicating a probable secondary event due to clonal evolution.

Child, Preschool↗
PubMed2004

Secondary chromosomal changes in 34 Philadelphia-chromosome-positive chronic myelocytic leukemia patients from the Mexican West.

The clonal evolution in t(9;22)-positive chronic myelocytic leukemia (CML) is well established. Four major changes occur in more than 70% of patients: +8, i(17q), +19, and an extra Philadelphia chromosome. The frequencies of secondary chromosomal changes in 34 patients from the states of Jalisco, Nayarit, Michoacán, and Colima (the Mexican West) with Philadelphia-chromosome-positive CML were assessed. The most frequent abnormalities were tetraploidy (12 cases); +8, inv(3)(q21q26), and octoploidy (3 cases each); and +der(22)(2 cases). Some translocations not previously associated with CML were observed, such as t(2;7)(p12;q36), t(3;6)(q26;p25), t(3;17)(q26;p13), and t(6;17)(q21;q23 approximately q25). Significant differences were found for +8 with respect to population results from Japan and from southern, eastern, and western Europe; for i(17)(q10) from eastern Europe; for +19 from Japan and western Europe; and for +der(22) from Japan, southern Europe, and western Europe. Although polyploidy could result from endomitosis, there is no direct evidence that the BCR/ABL protein influences such a process; however, protein kinases such as MAPK, which are involved in endomitosis, are activated by the BCR/ABL protein, and so the BCR/ABL protein could promote endomitosis through the MAPK pathway.

Adolescent↗
PubMed1997

Acquired monosomy 7 in donor cells in a patient treated for acute lymphoblastic leukemia with bone marrow transplantation.

Two years after a bone marrow transplant (BMT) from his haploidentical mother, a 28-year-old male with a history of acute lymphoblastic leukemia (ALI.) developed myelodysplastic syndrome (MDS) with monosomy 7 in his female bone marrow cells. Follow-up cytogenetic studies, including fluorescence in situ hybridization (FISH) performed twenty-seven and thirty-one months post-BMT consistently showed a female chromosome pattern with monosomy 7. Thirty-six and thirty-nine months post-BMT, further clonal evolution occurred, with the appearance of a sideline of the female cells that first expressed a del(10)(p11.2) and then developed a translocation, t(10;21)(p11.2;q22), in addition to the monosomy 7. Cytogenetic monitoring of this male patient helped to reveal a rare case of early MDS in transplanted donor cells and evolution of the acquired abnormal clone by identifying chromosomal alterations in the donated female bone marrow cells.

Adult↗
PubMed1999

Clinical implications of fluorescence in situ hybridization analysis in 13 chronic myeloid leukemia cases: Ph-negative and variant Ph-positive.

Thirteen chronic myeloid leukemia (CML) patients, 10 with variant Philadelphia (Ph) translocations and 3 Ph negative cases, were analyzed by fluorescence in situ hybridization (FISH) with the use of BCR and ABL cosmid probes and a chromosome 22 painting probe. In the variant Ph translocations, the BCR-ABL fusion gene was located on the Ph chromosome; in 1 CML Ph-negative patient, the BCR-ABL fusion gene was located on the Ph chromosome; and, in 2 patients, it was located on chromosome 9. The chromosome 22 painting probe was detected on the third-party chromosome of the variant translocation, and in none of the variant translocations was there any detectable signal on chromosome 9. In CML patients with clonal evolution of a simple Ph, a signal of the chromosome 22 painting probe was detected on the der(9) of the Ph translocation. It was concluded that the variant Ph translocations evolved simultaneously in a three-way rearrangement. The clinical parameters of the 13 patients were similar to those of a large group of CML patients with a simple Ph translocation. It is suggested that, to determine the prognosis of CML patients with a complex karyotype, FISH analysis with a chromosome 22 painting probe be performed.

Adult↗
PubMed2000

Tetrasomy 8 evolving into a segmental triplication 8q in a case of acute monocytic leukemia.

We report a case of AML-M5 with tetrasomy 8 that evolved within a 7-month period to a segmental triplication 8q. Other numerical abnormalities in the initial diagnosis were not found at the relapse; however, a chromosome 1 structural abnormality was maintained, proving the clonal evolution from tetrasomy 8 to a segmental triplication of the long arm of 8. This strongly suggests that there is a functional and selective advantage for duplications and triplications of 8q in these patients.

Aged↗
PubMed2000

Jumping translocations of 11q in acute myeloid leukemia and 1q in follicular lymphoma.

Jumping translocation is a rare cytogenetic aberration in leukemia and lymphoma, and its etiologic mechanisms are not clearly known. We report two cases with jumping translocations. One had follicular lymphoma and jumping translocations of 1q onto the telomeric regions of 5p, 9p, and 15q in three cell lines, co-existing with the specific translocation t(14;18)(q32;q21). The second case had acute myeloid leukemia (AML) and jumping translocations of 11q as the sole aberration, onto multiple derivative chromosomes in each of the abnormal cells. A total of 17 telomeric regions were seen as the recipients of 11q in this case, and 9q was always involved as one of the recipients in all abnormal cells. Fluorescence in situ hybridization (FISH) confirmed the identification of 11q material in the derivative chromosomes. While 1q has been the most common donor of acquired jumping translocations, this is the first report on jumping translocations of 11q. Different from all previously reported jumping translocations which involve only one recipient in each cell line and lead to a mosaic trisomy, multiple recipients in most of the abnormal cells in this case had led to a tetrasomy, or a pentasomy of 11q. The pattern of chromosome involvement as the recipients of 11q appears to show a continuing evolutionary process of jumping, stabilization, and spreading of the donor material into other chromosomes. Somatic recombinations between the interstitial telomeric or subtelomeric sequences of a derivative chromosome and the telomeric sequences of normal chromosomes are believed to be the underlying mechanism of jumping translocations and their clonal evolution.

Acute Disease↗
PubMed2000

Fanconi anemia: myelodysplasia as a predictor of outcome.

The adverse potential of the development of myelodysplastic syndrome (MDS) in Fanconi anemia (FA) was examined in a retrospective study of 41 FA patients who had bone marrow morphology and chromosomes reviewed by a single group. Thirty-three patients had adequate cytogenetic studies, and 16 (48%) had one or more abnormal studies: nine initially, and seven more on follow-up. Cytogenetic clonal variation was frequent, including disappearance of clones, clonal evolution, and appearance of new clones. The estimated five-year survival with a cytogenetic clone is 0.40, compared to 0.94 without a clone. Morphologic myelodysplasia (MDS), independent of a cytogenetic clone, was found in 13/41 patients (32%). The estimated five-year survival with MDS is 0.09, versus 0.92 without MDS. Leukemia developed in three patients whose initial cytogenetic clones prior to leukemia were t(1;18), t(5;22) and monosomy 7; the one with t(1;18) also had MDS. Our results focus on marrow morphology, and suggest that morphologic MDS may be more important than classical cytogenetics in prediction of an adverse outcome.

Adolescent↗
PubMed2000

Polysomy 13 with concomitant deletion of 13q13-14 involving the retinoblastoma gene and the D13S25 locus in a case of acute myeloid leukemia.

We herein describe a case of acute myeloblastic leukemia (AML), FAB subtype M4, with an unfavorable clinical course and a complex karyotype, including 4-9 copies of chromosome 13. Polysomy 13 was a result of clonal evolution. Fluorescence in situ hybridization (FISH) revealed a cytogenetically unrecognizable deletion within 13q13-14 that included the retinoblastoma gene (RB) and the D13S25 locus in all but one copy of chromosome 13. The only chromosome 13 that did not show a deletion affecting the q13-14 region was translocated to chromosome 7, resulting in a dic(7;13)(q21;p11). In this case, the coexistence of polysomy and a partial deletion within the same chromosome point toward a possible formation of a fusion product with oncogenic potential and its consecutive amplification as a critical alteration in this case.

Aged↗
PubMed2000

Late-appearing PML/RARalpha fusion transcript with coincidental t(12;13)(p13.2;q14) in acute promyelocytic leukemia lacking the t(15;17) cytogenetic anomaly.

The late appearance of a cytogenetic/molecular hallmark in human leukemias is a rare event. We report on a case of acute myeloid leukemia with morphology, immunophenotype and clinical features typical of promyelocytic subtype (APL), in which the specific PML/RARalpha gene rearrangement was molecularly detected only at second relapse of disease, without cytogenetic evidence of the t(15;17). The emergence of the PML/RARalpha gene may be therapy-related or may represent the exceptional result of a clonal evolution during progression of neoplasia. At second relapse, a novel cell clone bearing a t(12;13)(p13.2;q14) was also observed and a molecular deletion and rearrangement of a locus at 13q14, distinct from retinoblastoma (Rb1) locus, was found. In this unusual case, the PML/RARalpha product seems to be not essential for the expression of the promyelocytic phenotype at diagnosis and, when detectable, it is not the sole genetic defect.

Chromosomes, Human, Pair 12↗
PubMed2003

Evaluation of Trypanosoma cruzi hybrid stocks based on chromosomal size variation.

Although all classical lines of evidence point to the fact that Trypanosoma cruzi has a predominantly clonal evolution, accumulating data show that some T. cruzi stocks are the result of hybridisation events. We evaluated whether chromosomal polymorphism would give evolutionary information on hybrid isolates. Twenty-three coding sequences were mapped on the chromosomes of nine parasite stocks, four of which are putative hybrids (CL Brener and rDNA group 1/2). Phenetic analyses of karyotype data were based on the absolute chromosomal size difference index (aCSDI), a method that assumes that the genomic distance between two organisms is the sum of the size differences between their homologous chromosomes. aCSDI-based dendrograms obtained from a variable number of probes (3-18 probes) defined in all the cases three clusters: two corresponding, respectively, to T. cruzi I and T. cruzi II groups; and a third one, to rDNA group 1/2. CL Brener was alternatively positioned in T. cruzi II or rDNA group 1/2 clusters. Three clusters were also observed in the dendrogram constructed with restriction fragment length polymorphism (RFLP) data from 18 probes. The topology of the chromosome and RFLP dendrograms is similar, with a significant correlation coefficient (r=0.86062; P<0.0001), supporting a strong structuring of the clusters. This study also revealed that hybrid stocks have a larger proportion of two different-sized homologous chromosomes, as compared with non-hybrid strains. Overall, our results show that chromosomes are valuable characters for identification of evolutionary groups, in particular, T. cruzi hybrid organisms.

Animals↗
PubMed2001

Expression of P21(WAF1/CIP1/SID1) cyclin-dependent kinase inhibitor in hematopoietic progenitor cells.

P21(Waf1/Cip1/Sid1) is a critical component of biomolecular pathways leading to the G(1) arrest evoked in response to DNA damage, growth arrest signals and differentiation commitment. It belongs to the Cip/Kip class of cyclin-dependent kinase inhibitors and is at least partly regulated by p53. P21(Waf1/Cip1/Sid1) functional inactivation possibly resulting from mutations of the gene itself or, more likely, from p53 mutations may be critical for either the cell fate following DNA-damaging insults or clonal evolution toward malignancy. In the study presented here we describe a competitive polymerase chain reaction (PCR) strategy whose sensitivity and reproducibility enable us to attain a precise quantitation of p21(Waf1/Cip1/Sid1) expression levels in hematopoietic progenitors, the cell compartment which mostly suffers from the side effects of genotoxic drugs in use for cancer cure. The strategy was set in the M07 factor-dependent hematopoietic progenitor cell line. We confirmed that its p21(waf1/cip1/sid1) constitutive expression level is very low and up-modulated by DNA-damaging agents: ionizing radiations and ultraviolet light. Gene up-modulation resulted in checkpoint activation and, in particular, in a significant G(1) arrest, required for either the repair of damaged DNA sequences or apoptotic cell death. Our competitive PCR strategy was further validated in CD34(+) purified hematopoietic progenitors from healthy donors mobilized into the peripheral blood by granulocyte colony-stimulating factor and intended for allogeneic bone marrow transplantation. The constitutive p21(WAF1/CIP1/SID1) expression levels, measured in three separate harvests, were very low and no significant differences were apparent. Our results support the use of a competitive PCR strategy as a useful tool for clinical purposes, to assess the individual biomolecular response of early hematopoietic progenitors to antiblastic drugs.

Cell Cycle↗
PubMed1997

Telomere crisis in leukemia.

Previous studies on telomere dynamics in leukemia are summarized. The 'telomere crisis model' is proposed to explain the clonal evolution mechanism of cancer cells from the standpoint of telomere biology. Future trends, including the development of potential telomerase inhibitors as a new class of anti-cancer agent, are discussed.

DNA Damage↗