[Show abstract][Hide abstract] ABSTRACT: The MLL gene, located on chromosome band 11q23 is fused to different partner genes as a result of various chromosomal translocations in hematopoietic malignancies. A t(1;11) (q21;q23) resulting in a MLL-AF1q fusion gene has previously been reported. Cytogenetic studies on six cases are reported, including one three-way translocation. FISH analysis using a YAC encompassing the MLL gene and a YAC encompassing the AF1q locus showed splitting in three cases and two patients, respectively. PCR analysis of two cases confirmed that AF1q is specifically associated with t(1;11)(q21;q23). The MLL-AF1q fusion mRNA was similar to that previously described in one case and involved MLL exon 7 in the other. This study confirms the specific involvement of AF1q in t(1;11) (q21;q23)-positive acute leukemia with monocytic involvement.
[Show abstract][Hide abstract] ABSTRACT: A new case of translocation t(6;11)(q21;q23) in a patient with therapy-related acute myeloblastic leukemia is reported. The translocation results in fusion of the MLL and AF6q21 genes. The breakpoint with AF6q21 is located within the sequences encoding the AF6q21 fork head motif. The similar location of the localization of the chromosome 6 breakpoints in the present case and in the first case reported suggests their nonrandom localization. In addition, treatment for Hodgkin's disease prior to leukemia in both t(6;11)(q21;q23) cases suggests an association of this translocation with therapy-related leukemias, as reported for the recently described.
Genes Chromosomes and Cancer 08/1998; 22(3):221-4. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fusion genes implicating the MLL gene have been recently demonstrated in various 11q23 chromosomal abnormalities in human hematopoietic malignancies. We analyzed a t(6;11)(q21;q23) translocation detected in a secondary acute myeloblastic leukemia. This translocation results in fusion of the MLL gene on 11q23 to a previously unknown gene on chromosome 6 that differs from the previously reported MLL partner gene AF6q. The novel gene, named AF6q21, encodes a forkhead (FH) protein with strong similarities to the two FH family members whose genes are already known to be involved in chromosomal translocations of human malignancies, AFX and FKHR. Strikingly, in these translocations the breakpoints are located at the same position within the FH domains. Therefore, AF6q21, AFX, and FKHR could define a new FH subfamily particularly involved in human malignancies.
[Show abstract][Hide abstract] ABSTRACT: A novel class of conserved transcription factors has been identified from the molecular cloning of AF10, the gene involved in the t(10;11)(p12;q23) translocation of acute myeloid leukemias. AF10 encodes a 109-kD protein of 1,027 amino acids and contains an N-terminal zinc finger region and a C-terminal leucine zipper. These structures have been found to be conserved in sequence and position in three other proteins, AF17, BR140, and a previously unrecognized Caenorhabditis elegans gene, provisionally named CEZF. The overall structure, level of sequence conservation, and expression pattern suggest that these genes encode a new class of transcription factors, some of which are targets for chromosomal translocation in acute leukemia.
[Show abstract][Hide abstract] ABSTRACT: A patient with acute monocytic leukemia (AMoL) and t(6;11)(q27;q23) developed acute lymphoblastic leukemia (ALL) and t(4;11)(q21;23), 10 months after complete remission of the AMoL. The MLL gene, normally located at band 11q23, appeared differently rearranged in the cells of these two leukemias, showing a different origin for the two malignant clones. The responsibility of etoposide, used in treatment of the AML, in the occurrence of the ALL is probable in this patient.
[Show abstract][Hide abstract] ABSTRACT: A t(5;12)(q33;p13) translocation has been detected in two patients with myeloid disorder and eosinophilia. Six other patients with haematological disease with eosinophilia with similar translocation have been published previously. The existence of a new entity, a myeloproliferative disorder with eosinophilia and t(5;12) (q31-q33;p12-p13), is suggested by the results of the present study.
British Journal of Haematology 11/1994; 88(2):343-7. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A child with acute myelomonocytic leukemia, bone marrow eosinophilia and inv(16) received first-line therapy including etoposide (VP-16). Cytopenia and monocytosis appeared 7 months after complete remission while the child was treated with maintenance chemotherapy. Blood abnormalities persisted after discontinuation of treatment. Nine months after complete remission, t(11;11)(q13;q23) and HRX rearrangement were detected. Five months later, overt leukemia of monocytic type occurred. The responsibility of VP-16 therapy in this treatment-related acute myelocytic leukemia is discussed.
[Show abstract][Hide abstract] ABSTRACT: Rearrangements of the AML-1 gene on chromosome 21 as well as transcriptional expression of AML-1-ETO fusion gene were studied in 35 leukemic patients with t(8;21)(q22;q22). A panel of probes generated from the AML-1 gene regions flanking the breakpoint on chromosome 21 allowed us to detect the rearrangement in 24 out of 29 patients. A specific nested reverse transcriptase/polymerase chain reaction (RT/PCR) was developed to detect the t(8;21), either at diagnosis or as minimal residual disease. PCR amplification products were obtained in ten out of 11 patients investigated, and the sensitivity of the reaction was estimated to be between 1 x 10(4) and 1 x 10(-5) cell. An AML-1 rearrangement was also detected in one patient with 8q- and only one chromosome 21, but without 21q+. This indicated that the molecular rearrangement of the der(8) chromosome is more important than the reciprocal one in the malignant process.
[Show abstract][Hide abstract] ABSTRACT: Translocation t(3;22)(q27;q11) has recently been recognized as a recurrent abnormality in non-Hodgkin's malignant lymphoma (NHL). A new gene, LAZ3, has been shown to be involved in NHL with 3q27 rearrangement. Two patients with B-cell NHL were studied by chromosome painting and Southern blot analysis. Fluorescence in situ hybridization to metaphase chromosomes was shown to be an easy way to detect the chromosomal abnormality even in metaphase cells with poorly defined chromosomes. The gene LAZ3 was rearranged in one patient in the 'major translocation cluster region'. The comigration of rearranged LAZ3 and of IGL bands suggests that the translocation resulted in the juxtaposition of the two genes. This juxtaposition makes possible a potential deregulation of the LAZ3 gene expression, as previously shown for the MYC and BCL2 genes in Burkitt and follicular lymphoma translocations.
[Show abstract][Hide abstract] ABSTRACT: Nine KOX zinc finger genes were localized on four human chromosomes by in situ hybridization of cDNA probes to metaphase chromosomes. KOX1 (ZNF10), KOX11 (ZNF18), and KOX12 (ZNF19) were mapped to chromosome bands 12q24.33, 17p13-p12, and 16q22-q23, respectively. Six other KOX genes were localized on chromosome 19: KOX6 (ZNF14) and KOX13 (ZNF20) to 19p13.3-p13.2, KOX5 (ZNF13) and KOX22 (ZNF27) to 19q13.2-qter, and KOX24 (ZNF28) and KOX28 (ZNF30) to 19q13.4. Pulsed field gel electrophoresis experiments showed that the pairs of KOX genes found on the chromosome bands 12q24.33, 16q22-q23, 19p13.3-p13.2, or 19q13.3-qter lie within 200-300 kb DNA fragments. This suggests the existence of KOX gene clusters on these chromosomal bands.
Human Genetics 01/1994; 92(6):583-7. · 4.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two rearrangements affecting the same allele of the BCL2 gene were characterized by molecular analysis of an untreated follicular lymphoma. The first rearrangement interested the major breakpoint region (mbr) on chromosome 18 and a JH segment on chromosome 14. The other one was located at the 5' end of the BCL2 gene, in the so called variant cluster region (vcr), and consisted of a series of deletions that removed part of a DNA region where initiation of transcription normally occurs. Interestingly, both rearrangements involved the same BCL2 allele. The simultaneous presence of mbr (or mcr) translocations and of minor rearrangements in vcr has been previously suggested by restriction map analysis in a significant number of follicular lymphomas. The significance of these abnormalities on the oncogenic process is discussed.
[Show abstract][Hide abstract] ABSTRACT: A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.
Cancer Genetics and Cytogenetics 11/1993; 70(2):125-6. · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A t(9;11)(q33;q23) has been detected by chromosome painting with chromosome 11- and chromosome 9-specific probes in blast cells of a child with acute monocytic leukemia. Using a YAC clone spanning the usual breakpoint region of translocations of acute leukemias, it was shown that the breakpoint was effectively within the same region of the band 11q23. This was confirmed by Southern blot studies that showed the localization of the translocation breakpoint between the 6th and 8th exons of the HRX gene. The implication of the HRX gene in t(9;11)(q33;q23) is a novel example of the diversity of translocations involving this gene in hemopoietic disorders. Sequencing DNA in the vicinity of the breakpoints should help to understand the reason of the localization of the recombination hot spot at band 11q23.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 08/1993; 316(7):692-7.
[Show abstract][Hide abstract] ABSTRACT: We describe a patient with stage IV non-Hodgkin's lymphoma (NHL) and a t(11;18)(q21;q21) translocation. He presented with a gastric small B-cell lymphocytic lymphoma, expressing IgAL immunoglobulins without expression of CD10, CD5, and CD23 antigens. The lymphoma was the final development of a 6-year history of a monoclonal IgAL increase complicated by severe renal failure due to membranoproliferative glomerulonephritis. The clinical, histological, immunologic, and cytogenetic features of this patient are very similar to those observed in the five other patients with t(11;18) reported to date. This translocation therefore seems to delineate a new subtype of diffuse small B-cell lymphoma with involvement of mucosal sites. Involvement of the BCL2 oncogene on 18q21 could not be detected using molecular techniques with 5' as well as 3' BCL2 probes, indicating that other, so far unknown, genes relevant to lymphoid differentiation could be located in 18q21 and 11q21.
Genes Chromosomes and Cancer 06/1993; 7(1):54-6. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rearrangements of the BCL2 gene and expression of bcl-2 protein were analyzed in a series of 64 cases of follicular lymphomas in order to establish a relationship between the rearrangements and the protein overexpression. Of the 64 cases, 41 showed BCL2 rearrangement involving one of the three breakpoint clusters: 30 in mbr, eight in mcr, and three in vcr. A double rearrangement mbr+vcr was detected in two cases. Twenty cases with bcl-2 protein expression in tumor cells exhibited no apparent rearrangement, suggesting the possible existence of other mechanisms activating the gene. Interestingly, expression of the LMP1 protein, the Epstein-Barr virus (EBV) encoded gene, whose capacity to induce BCL2 has been recently demonstrated, was only found in 2/41 cases in which BCL2 was rearranged. These data suggest that EBV infection is not an important mechanism in the activation of BCL2 in follicular lymphoma.
[Show abstract][Hide abstract] ABSTRACT: Some recent aspects of the molecular biology of chromosome abnormalities that activate the BCL2 gene in B cell malignancies (follicular lymphoma, chronic lymphocytic leukemia) are discussed. We also report data showing that the Epstein-Barr virus (EBV) LMP-1 protein which can induce the expression of BCL2, is found infrequently in follicular lymphomas which exhibit no apparent BCL2 gene rearrangement.
Nouvelle revue française d'hématologie 03/1993; 35(1):37-40.
[Show abstract][Hide abstract] ABSTRACT: Acute promyelocytic leukemia (APL) is usually associated with the translocation t(15;17)(q22;q12-21), which disrupts the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. We report a patient with typical APL without the common t(15;17). Cytogenetic studies demonstrated a normal appearance of chromosomes 15, while a small marker seemed to be an i(17q-). Molecular analysis showed RARA and PML rearrangements, suggesting that the chromosome abnormality corresponded to a variant translocation.
Genes Chromosomes and Cancer 03/1993; 6(2):118-20. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously reported a 5' rearrangement of the BCL2 locus in a t(18;22) variant translocation found in a lymphocytic lymphoma. Primary structure analysis of both rearranged chromosomes confirmed the localization of the breakpoint in the so-called vcr region (for variant cluster region) that encompasses Z-DNA stretches 5' of the BCL2 locus, and in between J lambda 1 and C lambda 1 segments on the IGL locus. A 1,027 nucleotide segment from chromosome 22 was repeated on both derivative chromosomes 18q+ and 22q-. This segment contained an octanucleotide that was also present in the normal chromosome 18 close to the breakpoint. As a consequence of the translocation, a normal-sized BCL2 transcript was overexpressed in tumor cells.
Genes Chromosomes and Cancer 02/1993; 6(1):39-44. · 3.55 Impact Factor