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Abstract: A pericentric inv(9)(p22q34) of the derivative chromosome 9 that resulted from a standard t(9;22)(q34;q11.2) was identified by R-banding karyotypic analysis and fluorescence in situ hybridization (FISH) assays in 4 (0.18%) of 2,200 Philadelphia chromosome (Ph)-positive leukemia patients, including 3 with chronic myeloid leukemia (CML) in chronic phase and 1 with acute myeloid leukemia (AML) in our hospital since 2004. All four patients had two malignant clones: one with only t(9;22)(q34;q11.2) and another with der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) that resulted in the separation of the ABL1/BCR fusion gene. No metaphases with only inv(9)(p22q34) were seen in any of them. FISH also found a deletion of partial sequence of BCR on der(9)t(9;22)(q34;q11.2)inv(9)(p22q34) in 67.5% of bone marrow cells in the AML patient, but did not detect the deletion of the sequence of ASS/9q34 in these four patients. Reverse transcriptase–polymerase chain reaction revealed a b3a2 type of BCR/ABL1 fusion transcript in all of them, proving their disease to be Ph-positive leukemia. On reviewing the literature, only two solitary Ph-positive leukemia patients have been noticed to have the inv(9)(p22q34) anomaly. These two patients, together with our four documented patients, indicate that inv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Despite receiving hydroxyurea therapy (n = 3 patients), combined chemotherapy (n = 2), even imatinib treatment (n = 1), three patients, including one with AML and two with CML (one of whom progressed into the lymphoblastic blast phase), died with survival times of 28 days, 13 months, and 34 months, respectively. Only one patient with CML remained alive for 5.5 months. Their negative outcome implies that inv(9)(p22q34) has an unfavorable impact on prognosis. Presently, no firm conclusions can be drawn from this study. Because the case number reported here is very small, more patients with this anomaly need to be investigated to elucidate its true prognostic significance. [Copyright &y& Elsevier]

Abstract: To date, at least 25 translocations involving the NUP98 gene and different partner genes have been reported in the literature. Here, we describe a novel reciprocal t(5;11)(q31;p15) involving NUP98, as revealed by conventional karyotypic analysis using R-banding technique and fluorescence in situ hybridization (FISH) using a BAC RP11-120E20 probe and whole chromosome paint probes for chromosomes 5 and 11 in a 77-year-old woman who was diagnosed as having de novo acute myeloid leukemia. The patient received two courses of intensive combined chemotherapy but did not reach complete remission. She eventually died from the progressive disease, surviving for only 1 month after diagnosis. FISH analysis using WCP5 together with BAC RP11-878F9 or RP11-155N22 demonstrated that the breakpoint of chromosome 5 is located on 5q31. In addition, the EGR1 gene was unexpectedly found to be lost in the FISH study using EGR1 (red)/D5S23, D5S721 (green) dual-color probe. We supposed that the fusion gene created by t(5;11)(q31;p15) consisting of the NUP98 and its partner gene, as well as the loss of the EGR1 gene, may play a cooperative role in leukemogenesis. The partner gene of NUP98 in t(5;11)(q31;p15) is unclear at this time. Further molecular study is required to identify this partner gene in our patient. [Copyright &y& Elsevier]

Abstract: Translocation (14;14)(q11;q32) is one of the recurrent chromosome aberrations in ataxia-teleangiectasia (AT) and T-cell malignancies. In patients with the t(14;14), the TCL1 and TCRα/δ genes were found to be involved at the molecular level. However, t(14;14)(q11;q32) is an exceedingly rare phenomenon in B-lineage acute lymphoblastic leukemia (B-ALL). To date, it has been reported in only 5 B-ALL cases. Here, we report another B-ALL case with t(14;14)(q11;q32) in a 39-year-old female. The immunophenotype of the blasts showed positivity for CD79a, CD10, CD19, and HLA-DR. Chromosome analysis of the bone marrow (BM) cells at presentation showed the karyotype 47,XX,+4,t(14;14)(q11;q32). Fluorescence in situ hybridization (FISH) demonstrated trisomy 4 and the simultaneous involvement of the IGH gene at 14q32 and the CEBPE gene at 14q11, which differs from the genes involved in T-cell leukemias. After chemotherapy, the patient achieved complete remission (CR). Later, she received allogeneic peripheral blood stem cell transplantation. After CR, the karyotype of the BM cells was normal. She was disease-free at a 6-month follow-up. We suggest that t(14;14)(q11;q32) involving the IGH and CEBPE genes in B-ALL is rare, but it is a recurrent abnormality that could identify a new subgroup of B-ALL. [Copyright &y& Elsevier]

Abstract: The cytogenetic anomaly der(20)del(20)(q11.2q13.3)idic(20)(p11), or idic(20q−) in short form, has been reported in 13 cases of myelodysplastic syndrome, one case of chronic myelomonocytic leukemia, and one case of acute myeloid leukemia since 2004. To our knowledge, it has not previously been described in lymphoid diseases. Here we report the cases of two patients with B-cell acute lymphocytic leukemia (ALL) having a novel idic(20q−). One was a 34-year-old man with B-cell ALL whose leukemic cells at presentation had a karyotype of 45,XY,dic(9;20)(p11;q11.2); at relapse, a small marker chromosome was found coexisting with the dic(9;20). The other was a 39-year-old woman with Ph-positive B-cell-ALL whose leukemic cells contained both t(9;22)(q34;q11.2) and a small marker chromosome. A series of FISH analyses using the appropriate probes revealed the small marker chromosome in both patients to be an idic(20q−), confirming the dic(9;20)(p11;q11.2) in one case and revealing a BCR/ABL fusion gene in the other. One patient achieved complete remission but relapsed; the other did not achieve complete remission. Both patients died with a short survival time, despite receiving intensive chemotherapy. These two cases show that idic(20q−) can appear not only in myeloid diseases but also in lymphoid diseases. [Copyright &y& Elsevier]

Abstract: Translocations involving 21q22 are commonly observed in both de novo and therapy-related acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). They often result in the disruption of RUNX1 and give rise to fusion genes consisting of RUNX1 and different partner genes, which contribute to leukemogenesis. To date, at least 21 such translocations are known from the literature. Here we report two novel translocations involving the RUNX1 gene: t(1;21)(q12;q22) in a 53-year-old woman with AML-M5b and t(11;21)(q13;q22) in a 65-year-old man with AML-M2. The abnormalities revealed by R-banding karyotypic analysis were confirmed with interphase and metaphase fluorescence in situ hybridization (FISH), chromosome painting, and M-FISH. [Copyright &y& Elsevier]

Abstract: A clinical and experimental study of acute lymphoblastic leukemia (ALL) with a dic(7;9)(p11;p11) included 7 patients (5 males and 2 females) with a median age of 32 years. Cytogenetic analysis of bone marrow cells using an R-band technique showed a solitary dic(7;9) in 2 cases and a dic(7;9) accompanied by other abnormalities in 5 cases, of which 4 had also a t(9;22)(q34;q11). A minor breakpoint region (m-bcr) BCR/ABL rearrangement, corresponding to the fusion product gene p190, was detected by interphase FISH in 3 of these cases, Immunophenotyping analysis classified five of the 6 cases as B-lineage ALL. In 6 cases, FISH using whole chromosome painting (WCP) probes for chromosome 7 and 9 confirmed the reciprocal translocation between chromosomes 7 and 9; centromeric probes for chromosomes 7 and 9 confirmed the dicentric nature of the abnormal chromosome. The outcome of these ALL cases with simultaneous dic(7;9) and t(9;22) was worse than that of cases with an isolated dic(7;9). Our study brings the total number of published ALL cases with a dic(7;9) to 18. We consider the dic(7;9) a rare but recurrent abnormality, which may represent a distinct cytogenetic subgroup in B-ALL. [Copyright &y& Elsevier]

A rare chromosomal translocation, (11;20)(p15;q11), was detected in a 29-year-old male patient diagnosed with acute monocytic leukemia (AMoL) according to the French–American–British classification criteria. Whole chromosome painting analysis with paints for chromosomes 11 and 20 confirmed the result of conventional cytogenetic analysis. Reverse transcriptase polymerase chain reaction revealed the NUP98-TOP1 fusion transcript. To our knowledge, this is the second report of the translocation involving NUP98 and TOP1 genes in AMoL. On reviewing the literature, we suggest that t(11;20)(p15;q11) is associated with myelocytic disorders rather than lymphocytic proliferative diseases. [Copyright &y& Elsevier]