1/267. Development of acute promyelocytic leukemia with isochromosome 17q after BCR/ABL positive chronic myeloid leukemia.We describe a pediatric case of acute promyelocytic leukemia with an i(17q) after treatment of BCR/ABL positive chronic myeloid leukemia (CML) for 3.5 years. The patient was treated with Busulphan, alpha-2a interferon, hydroxyurea, and cytosine arabinoside at various times in the course of the chronic phase of CML, because he had no HLA-identical donor for bone marrow transplantation. Hematologic remission was achieved for a short time, but cytogenetic remission was never possible. When promyelocytic blast crisis was diagnosed according to the French-American-British classification, cytogenetic studies revealed an i(17q) as a new feature in our patient. The promyelocytic transformation was associated with the appearance of an i(17q) preceding CML are discussed in the light of recent literature.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
2/267. multiple myeloma preceding the development of chronic myelogenous leukemia.A case of a 70-year-old man who first developed multiple myeloma and then chronic myelogenous leukemia (CML) within a 3-year period is documented. The patient, with monoclonal hypergammopathy, was diagnosed with smoldering myeloma with IgG-kappa and bence jones protein kappa paraproteinemia. No chemotherapy was given for the myeloma until progressive leukocytosis developed after approximately 3 years. This was found to be due to philadelphia chromosome positive CML. A reverse transcription-polymerase chain reaction assay did not reveal BCR/ABL mRNAs when the myeloma was first diagnosed. The occurrence of 2 distinct hematologic malignancies in the same patient suggests either a different clonal evolution from a common pluripotent malignant stem cell since the CML stem cell also involves the B-lymphoid lineage, a coincident complication of the 2 hematological malignancies, or the coexistence of 2 distinct malignancies due to the same genetic background and/or exposure to similar carcinogenic agents. The literature provides support for the existence of a relationship between multiple myelomas and CML.- - - - - - - - - - ranking = 0.5keywords = leukemia (Clic here for more details about this article) |
3/267. Myeloperoxidase positive acute lymphoblastic leukemia cell lines, NALM-30, NALM-31 and NALM-32, carrying philadelphia chromosome with biphenotypic characteristics.We established three sister cell lines, NALM-30, NALM-31 and NALM-32, with biphenotypic features carrying myeloperoxidase mRNA and protein with complex Philadelphia (Ph) chromosome, t(9;22;10)(q34;q11;q22), from a patient with Ph-positive acute leukemia in relapse. Epstein-Barr virus nuclear antigen was negative. The morphological appearance of the cell lines is that of immature lymphoid cells. Expression of myeloid- and lymphoid-associated surface membrane antigens on these cells was detected allowing for the classification of "biphenotypic" leukemia. Immunophenotypically, the established cell lines reported here fulfill the European Group for the Immunological Characterization of Leukemias (EGIL) criteria for B-lineage derivation, however, surface and cytoplasmic immunoglobulin chains were negative. Whereas TGF-beta R (CD105), MCSFR (CD115), SCFR (CD117), IL-4R/IL-13R (CD124) and IL-6R (CD126) were not expressed, the cell lines were mostly positive for IFN-gamma R (CD119), IL-7R (CD127) and FLT-3R (CD135). The NALM-30, NALM-31 and NALM-32 cell lines together with their serial sister cell lines NALM-27 and NALM-28 which were established from the same patient at diagnosis provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic immature b-lymphocytes.- - - - - - - - - - ranking = 0.6keywords = leukemia (Clic here for more details about this article) |
4/267. Insertion of the 5' part of BCR within the ABL gene at 9q34 in a Philadelphia-negative chronic myeloid leukemia.We report a chronic myeloid leukemia patient without evidence of a Philadelphia (Ph) chromosome in whom RT-PCR analysis performed in blast crisis demonstrated the existence of both common b3a2 and b2a2 BCR/ABL fusion transcripts. in situ hybridization studies with BCR- and ABL-specific probes showed location of the BCR/ABL fusion gene on chromosome 9, band q34, instead of at chromosome 22q11, and that it resulted from an insertion of the 5' side of BCR within the ABL gene on chromosome 9. The vast majority of cells showed a BCR/ABL fusion gene on both chromosomes 9, which is equivalent to a double Ph chromosome, thus reinforcing the notion that the critical event in CML is the formation of a functional BCR/ABL fusion gene.- - - - - - - - - - ranking = 0.5keywords = leukemia (Clic here for more details about this article) |
5/267. Novel Philadelphia variant t(Y;9;22)(q12;q34;q11) in a case of chronic myeloid leukemia.A novel Philadelphia (Ph) variant translocation, t(Y;9;22)(q12;q34;q11), was detected in a 63-year-old man with a newly diagnosed chronic myeloid leukemia (CML). reverse transcription polymerase chain reaction (RT-PCR) analysis revealed a b3a2 fusion transcript. fluorescence in situ hybridization (FISH) utilizing library probes, subtelomeric cosmid probes, and probes hybridizing to the ABL and BCR genes showed a reciprocal three-way translocation involving Yq12, 9q34, and 22q11, and a BCR-ABL fusion signal on der(22). The subtelomeric Yq probe hybridizing centromerically to the IL9 receptor gene and covering the centromeric portion of the SYBL1 gene was found to be translocated to der(9).- - - - - - - - - - ranking = 0.5keywords = leukemia (Clic here for more details about this article) |
6/267. A new complex variant philadelphia chromosome, t(1;9;22)ins(17;22), characterized by fluorescence in situ hybridization in an adult ALL.A new complex variant philadelphia chromosome was detected in a 65-year-old man with acute, pre-B, lymphoblastic leukemia (ALL). The classic cytogenetic analysis identified an apparently balanced three-way translocation t(1;9;22)(q25;q34;q11.2). fluorescence in situ hybridization (FISH) studies confirmed the translocation and showed bcr/abl fusion on the der(22). However, these studies revealed that the distal part of the bcr gene was not translocated onto chromosome 1 at 1q25, but inserted into chromosome 17 at 17p12-13. This complex variant translocation was described as a t(1;9;22)(q25;q34;q11.2)ins(17;22)(p12-13;q11.2q11.2). Secondary changes including 8, an inversion of the derivative chromosome 9, a translocation t(14;20)(q11;q13), and an additional derivative 22 were also identified in most of the abnormal cells. The patient died from systemic fungemia and multiorgan failure 9 months after the diagnosis of ALL. The clinical significance of complex variant Philadelphia chromosomes in ALL is reviewed and discussed.- - - - - - - - - - ranking = 0.1keywords = leukemia (Clic here for more details about this article) |
7/267. Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation.dendritic cells (DCs) are believed to be the most potent antigen-presenting cells and may be important in the induction of anti-leukemia specific T cell responses. In this preliminary clinical study, a patient with chronic phase chronic myelogenous leukemia (CML) was vaccinated with autologous leukemic DCs following autologous peripheral blood stem cell transplantation (PBSCT). In an in vitro study, leukemic DCs were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha, and interleukin-4 from granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC fraction of this patient, and were found to be Ph1 , and to possess the morphologic and phenotypic characteristics of mature DCs. These cells could also elicit antigen specific immune responses, including a vigorous cytotoxicity specific to CML cells. In the clinical experiment, we obtained evidence that infused leukemic DCs could induce T cell clones expressing the same T cell receptor usage as a cytotoxic T cell line, suggesting that the immune repertoire includes tumor-reactive T cells. These cytotoxic T lymphocytes are activated in vivo. The vaccination of leukemic DC caused a decrease in the number of Ph1 cells in the peripheral blood and bone marrow. These results indicate that the activity is an immunologically mediated phenomenon and vaccination therapy with leukemic DC following autologous PBSCT may be effective in treating CML.- - - - - - - - - - ranking = 0.6keywords = leukemia (Clic here for more details about this article) |
8/267. Pre-B acute lymphoblastic leukemia with b3a2 (p210) and e1a2 (p190) BCR-ABL fusion transcripts relapsing as chronic myelogenous leukemia with a less differentiated b3a2 (p210) clone.The philadelphia chromosome translocation t(9;22)(q34;q11) may give rise to different BCR/ABL fusion mRNAs due to different genomic breakpoints and alternative splicing. The e1a2, b2a2 or b3a2 and c3a2 fusion mRNAs encode distinct fusion proteins (p190, p210 and p230, respectively), which are associated with different forms of leukemogenesis in humans and animal models. Our patient presented with acute pre-B cell lymphoblastic leukemia (ALL) with normal cytogenetics. After 3 years of standard ALL therapy, he relapsed with t(9;22)-positive chronic myelogenous leukemia (CML). Retrospective molecular analyses of the pre-treatment pre-B cell ALL sample showed the b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts. Only the b3a2 (p210) transcript was detected at relapse. Southern and immunoglobulin heavy chain (IgH) analyses of the presentation and relapse samples revealed an identical BCR rearrangement in both samples. However, only the ALL sample harbored an IgH gene rearrangement. These findings show a clonal relationship between the more differentiated pre-B cell and less differentiated CML clones and that the p210 and p190 fusion mRNAs were alternatively spliced from a single genomic breakpoint. Our patient's unusual molecular findings provide circumstantial evidence that the p190 protein may promote a more differentiated phenotype in a comparatively less differentiated p210-transformed precursor cell.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
9/267. Complex chromosome rearrangements may locate the bcr/abl fusion gene sites other than 22q11.BACKGROUND AND OBJECTIVE: From 5-8% of Philadelphia (Ph) positive patients with chronic myeloid leukemia (CML) show variant translocations in which at least a third chromosome in addition to 9q34 and 22q11 is involved. The formation mechanisms and clinical significance of variant Ph translocations are still unclear. The BCR/ABL chimeric gene encoding for chimeric proteins is always present and maps on the 22q- regardless of the type of translocation. We studied two apparently Ph negative CML patients with unusual karyotypes both showing a typical b3a2 rearrangement. DESIGN AND methods: Dual-color fluorescence in situ hybridization (FISH) can visualize BCR and ABL genes and localize the BCR/ABL fusion gene. We used FISH to study the formation mechanisms of variant Ph translocations in two patients. RESULTS: The chimeric BCR/ABL gene was located on a locus other than the expected 22q11 in both patients. In the first case the fusion signal was present on the 9q34 band whereas in the second patient it was detected on chromosome 8, involved in masked Ph formation. INTERPRETATION AND CONCLUSIONS: The location of the hybrid BCR/ABL gene on chromosomes other than 22q- is a rare event which can only be observed using the FISH technique. When these unusual translocations occur the hypothesis most often put forward is that several consecutive cytogenetic events have taken place. The factors which regulate the formation of these breakpoints have yet to be clarified. The FISH technique allows the identification of chromosome rearrangements that could not otherwise be detected by conventional banding procedures. The location of the hybrid BCR/ABL gene on sites other than 22q11 represents a rare type of variant Ph translocation.The real frequency and clinical significance of such rearrangements need to be investigated.- - - - - - - - - - ranking = 0.1keywords = leukemia (Clic here for more details about this article) |
10/267. Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature.This report describes two cases of philadelphia chromosome-negative (Ph(-)) non-Hodgkin's lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph( )) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkin's lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. dna obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(-) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph( ) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that 'Ph( ) NHL' occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph( ) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm. leukemia(2000) 14, 169-182.- - - - - - - - - - ranking = 0.6keywords = leukemia (Clic here for more details about this article) |
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