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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mixed-lineage leukaemia gene (MLL/HRX/ALL-1) is disrupted by chromosomal translocation in human acute leukaemias that often display mixed lymphoid-myeloid phenotypes and present in infancy. MLL possesses a highly conserved SET domain also found in Drosophila trithorax (trx) and Polycomb group (Pc-G) genes, which are known to regulate homeotic genes (HOM-C) in a positive or negative fashion, respectively. Mll was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its role in pattern development. Mll heterozygous (+/-) mice had retarded growth, displayed haematopoietic abnormalities, and demonstrated bidirectional homeotic transformations of the axial skeleton as well as sternal malformations. Mll deficiency (-/-) was embryonic lethal. Anterior boundaries of Hoxa-7 and Hoxc-9 expression were shifted posteriorly in Mll +/- embryos, but their expression was abolished in Mll -/- embryos. Thus Mll is required for proper segment identity in mammals, displays haplo-insufficiency, and positively regulates Hox gene expression.
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PMID:Altered Hox expression and segmental identity in Mll-mutant mice. 747 9

We report on three patients with acute non-lymphoblastic leukemia (ANLL) displaying the same chromosomal translocation t(11;15)(q23;q14). The clinical course of the disease was aggressive, and survival was short. The FAB subtype was M-2 in two cases, and M-1 in the remaining patient. Immunologically two cases showed aberrant expression of a lymphoid antigen (CD19 and TdT, respectively). HTRX1/MLL gene was rearranged in one patient studied at the time of diagnosis. These results plus data scattered in the literature show that the t(11;15)(q23;q14) can be added to the list of recurrent rearrangements in ANLL involving 11q23.
Leukemia 1995 Jul
PMID:Translocation (11;15)(q23;q14) in three patients with acute non-lymphoblastic leukemia (ANLL): clinical, cytogenetic and molecular studies. 763 Jan 91

The HRX gene has recently been shown to be involved in most of the chromosomal abnormalities of band 11q23 frequently present in human hematological malignancies. Rearrangements are strikingly diverse, but most affect a restricted area of the HRX gene and lead to gene fusion between HRX and a gene located on the partner chromosome. Another kind of HRX alteration seen in human acute leukemia is a partial duplication of the NH2 part of the HRX locus. We have characterized two cases of partial HRX duplication in acute leukemias bearing trisomy 11 as the sole chromosomal abnormality. In one patient analyzed at the genomic level, an Alu repeat was involved within exon 6 but not within intron 1. Splicing of exon 6 to exon 2 was observed in this patient while splicing of exon 8 to exon 2 was observed in the other. Our data indicated that HRX duplication is highly similar to the translocation affecting the HRX locus both in the restricted diversity of the fusion points and the involvement of Alu repeats within the breakpoint cluster region (exon 5 to 10).
Leukemia 1995 Sep
PMID:Partial duplication of HRX in acute leukemia with trisomy 11. 765 17

We examined clinical, morphologic, and cytogenetic features and ALL-1 (MLL, Htrxl, HRX) gene rearrangements in 17 cases of secondary leukemia that occurred 11 months to 9 years from diagnoses of primary cancers in children who received topoisomerase II inhibitors or developed secondary leukemias typical of those associated with this therapy. Primary diagnoses included nine solid tumors and eight leukemias. Ten secondary leukemias were acute myeloid leukemia (AML), one was of mixed lineage, two were acute lymphoblastic leukemia (ALL), and four presented as myelodysplasia. Of 15 cases with 11q23 involvement, 11 (73%) were cytogenetically identifiable; four cases had molecular rearrangement only. By Southern blot, rearrangements within the ALL-1 gene were similar to sporadic cases. The results of this analysis suggest the following: (1) In most pediatric cases of topoisomerase II inhibitor-associated leukemia, there is disruption of the breakpoint cluster region of the ALL-1 gene at chromosomal band 11q23. (2) Exposure histories vary in secondary 11q23 leukemia, as the only topoisomerase II inhibitor was dactinomycin in one case, and, in another case, no topoisomerase II inhibitor was administered. (3) There is clinical, morphologic, cytogenetic, and molecular heterogeneity in pediatric secondary 11q23 leukemia. (4) There are some survivors of pediatric secondary 11q23 leukemia, but the outcome is most often fatal.
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PMID:ALL-1 gene rearrangements in DNA topoisomerase II inhibitor-related leukemia in children. 775 57

We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months. The genomic configuration of ALL-1 in leukemic DNAs was determined by Southern blot hybridization and correlated with biological and clinical features at presentation, as well as with treatment outcome. Twenty-nine out of 45 (64%) patients showed ALL-1 rearrangements, including 4/11 (36%) infants aged between 13 and 18 months. Considering morphological types, 24/38 cases with acute lymphoblastic leukemia and 5/7 patients with acute myeloid leukemia showed ALL-1 rearrangements. The features more frequently found in association with ALL-1 rearrangements were hyperleukocytosis (P < 0.007) and CD19+/CD10- blast immunophenotype (P < 0.02). ALL-1 status was an independent prognostic marker of event-free survival (EFS) in a multivariate model including age, sex and WBC count, and maintained its statistical significance when FAB morphology was considered in the analysis by including AML patients. Considering the ALL cases the actuarial EFS was 57 and 9% for infants with germline and rearranged ALL-1 configuration, respectively (P = 0.008). A high frequency of ALL-1 gene alterations in infant AL is confirmed by this study. In addition, our results emphasize the need for extending the analysis of ALL-1 gene status to infants with AL aged > 12 months. We show that this genetic lesion is the most important variable negatively affecting prognosis in a multivariate model including other known risk factors. This latter observation should influence the choice of risk-adapted treatment strategies in this AL subset.
Leukemia 1995 Mar
PMID:Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias. 788 37

The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.
Leukemia 1994 Apr
PMID:Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11). 790 8

Breakpoints on chromosome 11 at band q23 have been observed in patients with primary or secondary leukaemia. Recent data have shown that these breakpoints are clustered in a approximately 15kb region of a gene named HRX. This gene product has homology to the Drosophila trithorax gene product, which suggests it may play a role in regulating transcription control. Disruption of HRX as a result of chromosomal translocation is thought to contribute to the leukaemogenic process; this may occur in utero giving rise to infant acute leukaemia or may be induced by epipodophyllotoxic drugs resulting in secondary leukaemia. Translocations of 11q23 can involve a number of different partner chromosomes. The reciprocal genes on chromosomes 4q21, 9p22 and 19p13 have been recently cloned and are predicted to encode proline and serine rich proteins. Of particular interest is the high degree of homology observed between the genes on 9p22 and 19p13, which suggests that they too may have an important role to play in the generation of the leukaemic phenotype.
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PMID:Chromosome 11q23 abnormalities in leukaemia. 792 Feb 16

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.
Leukemia 1994 Oct
PMID:Translocation t(11;11)(q13;q23) and HRX gene rearrangement associated with therapy-related leukemia in a child previously treated with VP16. 793 59

A patient with secondary acute myelomonocytic leukemia after treatment with chronic oral etoposide (VP-16) for lung cancer is reported. The leukemic cells showed a t(9;11)(p22;q23) translocation. Southern blot analysis revealed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a chimeric mRNA between the MLL gene at 11q23 and LTG9 (MLLT3/AF-9) gene at 9p22. The patient was successfully treated with a VP-16 based regimen. This case is instructive in the understanding of the leukemogenesis of VP-16-related leukemias.
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PMID:Acute myelomonocytic leukemia after treatment with chronic oral etoposide: are MLL and LTG9 genes targets for etoposide? 794 64

We report here an uncommon case of neonatal acute leukaemia that presented concomitant with serological evidence of rubella infection. The clinical course was aggressive and the patient died 5 days after diagnosis from septicaemia. Leukaemic blasts had a mixed lineage immunophenotype co-expressing a constellation of B-lymphoid (CD19, cytCD22, TdT) and myeloid (CD13, CD33, CD14, anti-MPO) markers, as well as multiple adhesion molecules and markers associated with early lympho-myeloid progenitor cells (CD34, CD7, HLA-DR). A previously unrecorded discordant expression of different CD10 and CD34 epitopes was identified using different monoclonal antibodies. The karyotype was 46,XX t(4;11)(q21;q23) and molecular analysis confirmed rearrangement of the trithorax-related oncogene HRX at 11q23. There was a clonal biallelic rearrangement of the immunoglobulin heavy-chain gene. The features of this rare case have implications for possible aetiological events leading to leukaemia.
Leukemia 1994 Jul
PMID:Neonatal mixed lineage acute leukaemia. 803 18


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