1/25. The inv(11)(p15q22) chromosome translocation of therapy-related myelodysplasia with NUP98-DDX10 and DDX10-NUP98 fusion transcripts.Chromosomal abnormalities involving the 11p15 or 11q22-23 bands have been reported in several types of human neoplasms including hematopoietic malignancies. The abnormalities are observed in therapy-related malignancies and less frequently in de novo myeloid malignancies. Abnormality of the MLL gene located on chromosome 11q23 has been well known in therapy-related myeloid malignancies, but it has been reported only recently that the inv(11)(p15q22) in de novo or therapy-related myeloid malignancies results in the fusion of NUP98 on chromosome 11p15 and DDX10 on chromosome 11q22. NUP98 is a nucleoporin that composes the nuclear pore complex and is the target gene in leukemia with the t(7;11)(p15;p15). The DDX10 gene encodes a putative adenosine triphosphate-dependent DEAD box rna helicase. Here we present another patient with acute myelocytic leukemia (M4) transformed from chronic myelomonocytic leukemia with the inv(11) chromosome who had been treated with etoposide for a germ cell tumor. By reverse transcription polymerase chain reaction (RT-PCR) of the rna from the leukemic cells of the patient, DDX10-NUP98 and NUP98-DDX10 fusion transcripts were detected. Our case confirms that the inv(11) is a rare chromosomal translocation that is associated with therapy-related or de novo myeloid malignancy and involves NUP98 and DDX10 but not MLL. RT-PCR of the fusion transcripts might be applied to the detection of a small number of leukemic cells in the bone marrow or blood of patients in remission or in the cells harvested for autologous transplantation.- - - - - - - - - - ranking = 1keywords = complex, neoplasm (Clic here for more details about this article) |
2/25. A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer cytogenetics Group (UKCCG)Partial deletion of the long arm of chromosome 5, del(5q), is the cytogenetic hallmark of the 5q-syndrome, a distinct subtype of myelodysplastic syndrome-refractory anemia (MDS-RA). Deletions of 5q also occur in the full spectrum of other de novo and therapy-related MDS and acute myeloid leukemia (AML) types, most often in association with other chromosome abnormalities. However, the loss of genetic material from 5q is believed to be of primary importance in the pathogenesis of all del(5q) disorders. In the present study, we performed fluorescence in situ hybridization (FISH) studies using a chromosome 5-specific whole chromosome painting probe and a 5q subtelomeric probe to determine the incidence of cryptic translocations. We studied archival fixed chromosome suspensions from 36 patients with myeloid disorders (predominantly MDS and AML) and del(5q) as the sole abnormality. In 3 AML patients studied, this identified a translocation of 5q subtelomeric sequences from the del(5q) to the short arm of an apparently normal chromosome 11. FISH with chromosome 11-specific subtelomeric probes confirmed the presence of 11p on the shortened 5q. Further FISH mapping confirmed that the 5q and 11p translocation breakpoints were the same in all 3 cases, between the nucleophosmin (NPM1) and fms-related tyrosine kinase 4 (FLT4) genes on 5q35 and the Harvey ras-1-related gene complex (HRC) and the radixin pseudogene (RDPX1) on 11p15.5. Importantly, all 3 patients with the cryptic t(5;11) were children: a total of 3 of 4 AML children studied. Two were classified as AML-M2 and the third was classified as M4. All 3 responded poorly to treatment and had short survival times, ranging from 10 to 18 months. Although del(5q) is rare in childhood AML, this study indicates that, within this subgroup, the incidence of cryptic t(5;11) may be high. It is significant that none of the 24 MDS patients studied, including 11 confirmed as having 5q-syndrome, had the translocation. Therefore, this appears to be a new nonrandom chromosomal translocation, specifically associated with childhood AML with a differentiated blast cell phenotype and the presence of a del(5q).- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
3/25. trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with 11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.- - - - - - - - - - ranking = 3.4165916970757keywords = complex (Clic here for more details about this article) |
4/25. Acute myelomonocytic leukemia with histologic features resembling sarcomatoid carcinoma in bone marrow.We report a case of primary acute myelomonocytic leukemia involving the bone marrow that resembled sarcomatoid carcinoma. The neoplastic cells in bone marrow biopsy specimens formed cohesive-appearing clusters and cords separated by an immature fibroblastic proliferation and myxoid stroma. Blasts in the bone marrow aspirate smears formed clusters and sheets, and a subset of blasts exhibited erythrophagocytosis. Dysgranulopoiesis was also present. Lineage was confirmed by immunohistochemical analysis of formalin-fixed, paraffin-embedded tissue. The tumor cells showed strong reactivity for lysozyme, myeloperoxidase, CD45, and CD68 and were negative for keratin, S100, CD20, and CD3. The serum lysozyme concentration (110 microgram/mL) was 13 times greater than the normal value (8 microgram/mL). Cytogenetic studies performed on bone marrow aspirate material revealed a complex karyotype, including trisomy 8 and abnormalities of chromosome 11q. We report this case of acute myelomonocytic leukemia because the neoplastic cells appeared cohesive and spindled, resembling sarcomatoid carcinoma, and therefore caused diagnostic difficulty. Other monocytic neoplasms with similar resemblance to carcinoma or sarcoma have been reported in the literature, suggesting that the tendency to appear cohesive may be an inherent characteristic of neoplastic cells with monocytic differentiation.- - - - - - - - - - ranking = 1keywords = complex, neoplasm (Clic here for more details about this article) |
5/25. 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.- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
6/25. CBFB/MYH11 fusion in a patient with AML-M4Eo and cytogenetically normal chromosomes 16.We present a unique case of acute myeloid leukemia M4Eo (AML-M4Eo) with a CBFB/MYH11 fusion transcript and a trisomy 22, but in whom cytogenetic analyses did not disclose an inv(16). fluorescence in situ hybridization (FISH) analysis with chromosome arm-specific painting probes as well as with the c40 and c36 cosmids also revealed no evidence for an inv(16), whereas the application of locus-specific probes confirmed the presence of a masked inv(16). The results of our comprehensive FISH investigations indicate that the events leading to this masked inv(16) were complex and concurred with deletions on both the long and short arms. The most likely explanation for the formation of the relevant CBFB/MYH11 fusion is an insertion of parts of the MYH11 into the CBFB gene, although it is also possible that it was formed by a double inversion.- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
7/25. A novel variant three-way translocation of inversion 16 in a case of AML-M4eo following low dose methotrexate therapy.We report a case of acute myelomonocytic leukemia with eosinophilia (AML-M4eo) in a 65-year-old man following low dose methotrexate treatment for pemphigus vulgaris. Cytogenetic studies at diagnosis revealed a complex karyotype including a reciprocal translocation between 11q14.2 and 16q22, an inversion of chromosome 16(p13.1q22), and an apparently terminal deletion of 7q31. The presence of inv(16) was confirmed by reverse transcription-polymerase chain reaction which demonstrated a Type A fusion transcript derived from the core binding factor (CBF) beta and the smooth muscle myosin heavy chain (MYH11) genes. The patient was in complete hematologic and cytogenetic remission 6 months following intensive chemotherapy. Because AML-M4eo with inv(16) has a favorable prognosis, molecular studies should be performed in case the identification of inv(16) by conventional cytogenetics is difficult due to a complex karyotype.- - - - - - - - - - ranking = 1.3666366788303keywords = complex (Clic here for more details about this article) |
8/25. The human formin-binding protein 17 (FBP17) interacts with sorting nexin, SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia.We have cloned a fusion partner of the MLL gene at 11q23 and identified it as the gene encoding the human formin-binding protein 17, FBP17. It maps to chromosome 9q34 centromeric to ABL. The gene fusion results from a complex chromosome rearrangement that was resolved by fluorescence in situ hybridization with various probes on chromosomes 9 and 11 as an ins(11;9)(q23;q34)inv(11)(q13q23). The rearrangement resulted in a 5'-MLL/FBP17-3' fusion mRNA. We retrovirally transduced murine-myeloid progenitor cells with MLL/FBP17 to test its transforming ability. In contrast to MLL/ENL, MLL/ELL and other MLL-fusion genes, MLL/FBP17 did not give a positive readout in a serial replating assay. Therefore, we assume that additional cooperating genetic abnormalities might be needed to establish a full malignant phenotype. FBP17 consists of a C-terminal Src homology 3 domain and an N-terminal region that is homologous to the cell division cycle protein, cdc15, a regulator of the actin cytoskeleton in schizosaccharomyces pombe. Both domains are separated by a consensus Rho-binding motif that has been identified in different Rho-interaction partners such as Rhotekin and Rhophilin. We evaluated whether FBP17 and members of the Rho family interact in vivo with a yeast two-hybrid assay. None of the various Rho proteins tested, however, interacted with FBP17. We screened a human kidney library and identified a sorting nexin, SNX2, as a protein interaction partner of FBP17. These data provide a link between the epidermal growth factor receptor pathway and an MLL fusion protein.- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
9/25. Acute myeloblastic leukaemias of FAB types M6 and M4, with cryptic PML/RARalpha fusion gene formation, relapsing as acute promyelocytic leukaemia M3.Demonstration of either the translocation t(15;17)(q22;q21) or the fusion of PML and RARalpha genes is regarded as diagnostic for acute myeloid leukaemia (AML) of FAB type M3, but has occasionally been seen in other FAB types. We present two such cases. Case 1 presented with FAB type M6 and a complex karyotype involving chromosomes 1, 2, 11 and 17. Bone marrow relapse of FAB type M3 followed autologous bone marrow transplantation. Subsequent marrow dysplasia and an M6 relapse were accompanied by a new cytogenetic clone involving chromosomes X, 2, 4, 6, 7 and 16. fluorescence in situ hybridization (FISH) of metaphase chromosomes at diagnosis showed insertion of material from chromosome 17 into a 'normal' 15 with juxtaposition of PML and RARalpha. Case 2 presented as AML M4 and relapsed as M3. cytogenetic analysis at diagnosis and in relapse showed 46,XY,t(15;17)(q22;q11),del(16)(q22). FISH analysis showed this to be a three-way translocation involving chromosomes 15, 16 and 17 again with juxtaposition of PML and RARalpha. reverse transcription-polymerase chain reaction (RT-PCR) revealed PML/RARalpha fusion at diagnosis, in remission and in first relapse. These examples strengthen the case for RT-PCR screening of all AML patients for these fusion genes.- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
10/25. Transient hematologic and clinical effect of E21R in a child with end-stage juvenile myelomonocytic leukemia.E21R is a modified granulocyte macrophage-colony-stimulating factor (GM-CSF) protein which results in antagonism of GM-CSF function via selective binding to the GM-CSF receptor complex. Juvenile chronic myelomonocytic leukemia (JMML) is a rare leukemia where spontaneous proliferation of myeloid and monocytic precursors in patients' bone marrow cultures is dependent on GM-CSF. For patients who progress after systemic chemotherapy, there are no effective therapies. in vitro and in vivo studies in an animal model demonstrating that E21R exerts an antileukemic action prompted us to consider its potential utility in a child with end-stage JMML. E21R was well-tolerated during the 3 courses of subcutaneous treatment. A clear in vivo efficacy was observed after 2 courses of E21R but the disease appeared completely refractory during the third course. This novel therapeutic approach clearly deserves further evaluation in JMML.- - - - - - - - - - ranking = 0.68331833941514keywords = complex (Clic here for more details about this article) |
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