1/16. Chromosome 16 inversion-associated translocation: two new cases.Two patients with chromosome 16 inversion-associated translocation were studied with conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques. The same chromosome 16 was involved in inversion and translocation in both patients. The chromosome translocation breakpoint was located within the heterochromatin of chromosome 16 but outside the alpha satellite domain in the t(10;16) of the first patient, whereas it was outside the heterochromatin area in the second case with t(1;16). These two types of rearrangements may be due to different mechanisms and illustrate the possible difficulties in recognizing the chromosome 16 inversion without FISH studies.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/16. Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia.BACKGROUND AND OBJECTIVES: The ETV6 gene undergoes rearrangements with tyrosine kinases in hematologic malignancies and solid tumors. ETV6/ABL1 chimeric proteins have been detected both in lymphoid and myeloid disorders. Our objective was to study two new cases of ETV6/ABL1-positive acute myeloid leukemia (AML) and to focus on bone marrow morphology and on molecular cytogenetics of eosinophilic cells. DESIGN AND methods: fluorescence in situ hybridization (FISH) was performed in two AML cases with different translocations, i.e. t(8;12)(p21;p13) and t(9;12) (q34; p13). We used probes for the short arm of chromosome 12, for ABL1 and BCR, for centromeric regions, and for whole chromosome arms. Polymerase chain reaction (PCR) was carried out by applying primers selected for the ETV6 gene. RESULTS: In both cases, bone marrow morphology was characterized by trilineage dysplasia and increased abnormal eosinophils. FISH showed the 5'ETV6 translocated to chromosome 8 in patient #1, and to chromosome 9 in patient #2. A 3' PCR identified chimeric products resulting from fusion between ETV6 exon 4 or exon 5, and ABL1 exon 2. Accordingly, an ETV6/ABL1 fusion signal was detected on der(8) in patient #1, and on der(9) in patient #2. Using interphase FISH abnormal bone marrow eosinophils were proved to belong to the neoplastic clone, carrying the ETV6 rearrangement. INTERPRETATION AND CONCLUSIONS: Our findings provide new information on the heterogeneity of conventional cytogenetics in ETV6/ABL1 positive leukemias, and indicate the putative target cell in this AML is an immature precursor capable of terminally differentiating towards eosinophils.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/16. Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature.Chronic myelocytic leukemia (CML) is a chronic myeloproliferative disorder characterized by cytogenetic or molecular evidence of philadelphia (Ph) chromosome, t(9;22)(q34;q11). Mild to moderate eosinophilia is commonly seen in CML. However, eosinophilia as a dominant feature of CML is extremely rare. We describe a case of Ph(-) CML with eosinophilia. Loeffler endocarditis, and t(9;12)(q34;p13) that resulted in an ETV6-ABL gene rearrangement/fusion identified to the best of our knowledge, for the first time by using commercially available fluorescence in situ hybridization probes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/16. A complex variant t(8;21) involving chromosome 3 in a child with acute myeloblastic leukemia with eosinophilia (AML M4Eo).Although the classic t(8;21) has been reported in 10 pediatric patients with acute myeloid leukemia with eosinophilia (AML M4Eo), no complex variant t(8;21) in children with AML M4Eo has been previously described. In our analysis of leukemic blasts from a 4-year-old boy with AML M4Eo, conventional cytogenetics revealed that 95% of the cells had a hypodiploid line containing 45 chromosomes and a complex karyotype involving chromosomes 3, 8, and 21. fluorescence in situ hybridization using whole chromosome painting probes for these chromosomes confirmed the cytogenetic findings. The presence of a CBFA2-ETO fusion gene was established by fluorescence in situ hybridization and reverse-transcriptase polymerase chain reaction analysis. Thus, this report illustrates the first description of a complex variant t(8;21) involving chromosome band 3q27 in a child with AML M4Eo.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
5/16. Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib.eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities of chromosome band 5q31-33, including those that present with t(1;5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and affect patient survival. We cloned the t(1;5)(q23;q33) and showed that it fuses platelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil domains of a novel partner protein, myomegalin. Using two-color interphase fluorescence in situ hybridization (FISH), we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started, complete clinical and hematologic remission, as well as major cytogenetic response, was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/16. p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder.We describe the fusion of TP53BP1 to PDGFRB in a patient with a chronic myeloid leukemia-like disorder associated with eosinophilia and a t(5;15)(q33;q22). TP53BP1 encodes 53BP1, a p53-binding protein that plays a role in cellular responses to dna damage. The 53BP1-PDGFRbeta fusion protein is predicted to retain the kinetochore-binding domain of 53BP1 fused to the transmembrane and intracellular tyrosine kinase domain of PDGFRbeta. The presence of the fusion was confirmed by two-color fluorescence in situ hybridization, reverse transcription-PCR, and by characterizing the genomic breakpoints. The reciprocal fusion, which would contain the p53-binding 53BP1 BRCA1 COOH-terminal domains, was not detectable by fluorescence in situ hybridization or nested PCR. Imatinib, a known inhibitor of PDGFRbeta, blocked the growth of patient colony-forming unit, granulocyte-macrophage in vitro and produced a clinically significant response before relapse and subsequent death with imatinib-resistant disease. We conclude that TP53BP1-PDGFRB is a novel imatinib target in atypical chronic myeloid leukemia.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
7/16. A case of chronic myelomonocytic leukemia with severe eosinophilia having t(5;12)(q31;p13) with t(1;7)(q10;p10).We describe an unusual case of chronic myelomonocytic leukemia with severe eosinophilia having t(5;12)(q31;p13) with t(1;7)(q10;p10). The eosinophilic proliferation was severe in peripheral blood and bone marrow, and they revealed marked dysplastic features. We performed fluorescence in situ hybridization (FISH) and immunohistochemistry to evaluate the clonality of eosinophils. The eosinophils were stained positively to platelet-derived growth factor receptor-beta. By FISH using chromosome 1 satellite probe and chromosome 1q telomere probe, the eosinophils were proved to belong to the malignant clone.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/16. Development of diffuse fasciitis with eosinophilia during L-tryptophan treatment: demonstration of elevated type I collagen gene expression in affected tissues. A clinicopathologic study of four patients.We describe the cases of four women who developed a scleroderma-like syndrome during L-tryptophan treatment for insomnia or tinnitus. The illness was characterized by swelling of the extremities, skin rash, myalgia, and elevation of the peripheral blood eosinophil count, followed by rapidly progressive cutaneous and subcutaneous induration. The histopathologic examination of affected skin showed thickening of the fascia, deep dermal fibrosis, and accumulation of mononuclear cells and abundant eosinophils. The expression of the type I procollagen gene was examined by in-situ hybridizations of affected skin with a human sequence-specific complementary DNA (cDNA). Increased hybridization signals were detected in the deep dermis and fascia, indicating enhanced expression of the collagen gene. The temporal association of L-tryptophan use and the development of a scleroderma-like illness in these four patients suggests a causal relation between L-tryptophan or its metabolites and the stimulation of fibroblast collagen gene expression that results in dermal and fascial fibrosis.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
9/16. Power of the MAC (morphology-antibody-chromosomes) method in distinguishing reactive and clonal cells: report of a patient with acute lymphatic leukemia, eosinophilia, and t(5;14).We present a patient with acute lymphatic leukemia, eosinophilia, and a 5;14-translocation, a rare but well-documented condition. In order to clarify whether granulocytes were involved in the disease, we applied the MAC (Morphology-Antibody-chromosomes) technique to samples of the bone marrow and, during a central nervous system relapse, to those of the cerebrospinal fluid. The karyotype of the blast cells was 47,XY, X,t(5;14)(q31;q32),i(7)(q10). interphase cytogenetic study by in situ hybridization with an X-specific alphoid probe revealed the abnormality in CD10, CD19, and TdT (terminal deoxynucleotidyl transferase) positive lymphoid cells, whereas CD13 positive, sudan black B positive, eosinophilic, and basophilic granulocytes as well as monocytes and small lymphocytes did not have the abnormality. Our results show that the eosinophilic and basophilic granulocytes in this subtype of acute leukemia do not belong to the malignant clone but are reactive. This study also confirmed the usefulness of the MAC technique in distinguishing neoplastic and reactive cells in malignancy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/16. Refractory cytopenia with t(1;7), 8 abnormality and dysplastic eosinophils showing intranuclear Charcot-Leyden crystals: a fluorescence in situ hybridization study.A case of refractory cytopenia and marrow eosinophilia showing t(1;7) translocation and concomitant trisomy 8 is reported. The eosinophils were dysplastic, and showed the unique feature of intranuclear Charcot-Leyden crystal formation, giving rise to a 'lip-like' appearance. We speculate that this unusual cytologic feature resulted from abnormal precipitation of Charcot-Leyden crystal protein in the eosinophils. By fluorescence in situ hybridization using a chromosome 8 specific alpha-satellite probe, the abnormal eosinophils were shown to have derived from the abnormal clone. We postulate that the dysplastic clone might have retained a differentiation potential and be responsive to normal haemopoietic stimuli.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
| | Next -> |