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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unbalanced translocations as well as interstitial deletions of the short arm of chromosome 12 [del(12p)] are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. These changes result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome containing the TEL gene, a cosmid contig containing part of TEL and a P1 contig containing the KIP1 gene to 12p13. These probes were used for fluorescence in situ hybridization to analyze samples from 47 patients with various hematologic malignancies who had unbalanced translocations (25 patients) leading to loss of 12p or deletions (22 patients) involving 12p13. The patients had acute lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy-related MDS or AML (7 cases), non-Hodgkin's lymphoma (2 cases), and other hematopoietic malignancies (5 cases). All three probes were hemizygously detected in 26 cases and were completely retained in only 9 cases. In 12 cases probes for one of the two genes were deleted, allowing us to map the smallest region of overlap of these deletions to a small genomic region that is bordered on the telomeric side by the TEL gene and on the centromeric side by KIP1. The genomic distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp.
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PMID:TEL and KIP1 define the smallest region of deletions on 12p13 in hematopoietic malignancies. 763 60

In myeloid and lymphoid leukemias recurrent chromosomal aberrations can be detected in chromosome region 12p13. We characterized the genes involved in t(12;22) (p13;q11) in two patients with myeloid leukemia and one with myelodysplastic syndrome (MDS). MN1, a gene on chromosome 22q11 was shown to be fused to TEL, a member of the family of ETS transcription factors on chromosome 12p13. The translocation results in transcription of the reciprocal fusion mRNAs, MN1-TEL and TEL-MN1, of which MN1-TEL is likely to encode an aberrant transcription factor containing the ETS DNA-binding domain of TEL. In addition to fusion of TEL to the PDGF beta receptor in t(5;12) in chronic myelomonocytic leukemia (CMML), our data suggest that the involvement of this protein in myeloid leukemogenesis could be dual; its isolated protein-protein dimerization and DNA-binding domains may be crucial for the oncogenic activation of functionally different fusion proteins.
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PMID:Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11. 773 5

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet-derived growth factor receptor-B gene on chromosome 5 and a novel ETS-like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.
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PMID:TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13). 774 47

We have identified a new recurrent reciprocal translocation between chromosome 3 and 12 with breakpoints at bands 3q26 and 12p13, t(3;12)(q26;p13) in the malignant cells from five patients with acute transformation of myelodysplastic syndrome or blast crisis of chronic myelogenous leukemia. t(3;12)(q26;p13) appears as a rare but nonrandom event present in various myeloid leukemia subtypes, which is frequently associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and a very poor prognosis. Here, we report the molecular cytogenetic analysis of the t(3;12). Fluorescence in situ hybridization results indicate that the 3q26 breakpoints are quite heterogeneous and occur 5' of MDS1, 3' of EVI1, or between MDS1 and EVI1. Our results are very similar to those observed in other 3q26 rearrangements in which breakpoints were shown to occur over considerable distances 5' and 3' of EVI1. Fluorescence in situ hybridization investigations proved that, in three myelodysplastic syndrome cases with t(3;12)(q26;p13), the 12p 13 breakpoint occurred within the TEL gene.
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PMID:Fluorescence in situ hybridization analysis of t(3; 12)(q26; p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes. 869 16

We identified a fusion between ETV6 on 12p13 and MDS1/EVI1 on 3q26 in a t(3;12)(q26;p13) found in two cases of myeloproliferative disorder. The resulting chimeric transcript consists of the first two exons of ETV6 fused to MDS1 sequences, which in turn is fused to the second exon of the EVI1 gene. It has recently been reported that MDS1 can be expressed in normal tissues both as a single gene and fused to EVI1. ETV6 does not contribute any known functional domain to the predicted fusion protein. Association with blast crisis and myelodysplastic syndrome-derived leukemia, bad prognosis, and relative complex karyotype are in agreement with observations made in other cases of t(3;12)(q26;p13). Furthermore, a comparison can be made with the formation of an AML1/MDS1/EVI1 fusion gene in translocations (3;21)(q26;q22).
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PMID:Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. 904 25

Seventy-nine acute myeloid leukemias (AML) and myelodysplastic syndromes without cytogenetic evidence of 12p aberrations were investigated by fluorescence in situ hybridization with probes for ETV6 and CDKN1B (previously called TEL and KIP1, respectively) to ascertain whether abnormalities of these genes are frequently undetected by standard chromosome banding analyses and, if so, whether they are associated with specific karyotypic patterns and morphologic features. One of sixty cytogenetically aberrant myeloid malignancies, an AML with a complex karyotype including del(5q) and del(20q), showed a hemizygous interstitial deletion of the ETV6 and CDKN1B loci. No concomitant rearrangement of the other ETV6 allele was detected. Two of nineteen cytogenetically normal AML displayed a hemizygous interstitial deletion involving CDKN1B, but not ETV6. Thus, cryptic deletions of these genes seem to be rare in cytogenetically abnormal myeloid malignancies without 12p aberrations (2%), whereas they may be more frequent in karyotypically normal AML (10%). Furthermore, the present findings show that the deletions may be narrow, not including the ETV6 gene, and indirectly suggest that CDKN1B, or a closely located genomic segment, is the target of 12p deletions.
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PMID:Deletions of CDKN1B and ETV6 in acute myeloid leukemia and myelodysplastic syndromes without cytogenetic evidence of 12p abnormalities. 917 97

Few genes have a proven role in the pathogenesis of myelodysplastic syndromes (MDS). The most common abnormalities involve the RAS genes, most notably the N-RAS gene, and are present in 10% of cases at diagnosis and in 30% to 40% during the course of the disease. Mutations of the p53 are found in 5% to 10% of cases. Mutations of the cFMS genes are less common, abnormalities of the NF1 genes seem to occur only in children, and abnormalities of the RB genes are exceedingly rare. A few instances of t(5;12) or t(3;21) translocation have been demonstrated, and their study has provided evidence that the TEL, EVI1, MDS1, and AML1 genes are involved in some cases of MDS. The presence in MDS of recurrent chromosome 7, 5q, and 20q deletions suggests that these chromosomal segments may bear tumor suppressor genes involved in MDS. The gene(s) involved remain(s) to be identified. Clonality studies have shown that stem cell involvement usually occurs at the myeloid level and that normal multipotent stem cells persist in many patients with MDS. This opens up the promising possibility that transplantation of autologous multipotent stem cells may be an effective therapeutic approach.
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PMID:[Molecular abnormalities and clonality in myelodysplastic syndromes]. 940 79

We have used Southern blotting and fluorescence in situ hybridization (FISH) to define the breakpoints of a reciprocal translocation, t(10;12)(q24;p13), acquired as a secondary abnormality in a patient with Philadelphia chromosome positive chronic myeloid leukemia (CML) in transformation. A YAC clone that spanned the breakpoint at 12p13 was identified; this YAC included the CDKN1B gene but did not include ETV6. Neither ETV6 nor CDKN1B was rearranged, as determined by FISH and Southern blotting; however, a small deletion encompassing the translocated CDKN1B allele was detected. Analysis of two candidate genes at 10q24, HOX11 and NFKB2 suggested that they are not involved in this translocation. The preliminary mapping of breakpoints in this case demonstrated that they are different from an apparently identical translocation identified previously in a patient with myelodysplastic syndrome. The identification of the split YAC and small deletion should enable a more focused search for a gene or genes that may contribute to progression from chronic phase to blast crisis in CML.
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PMID:Characterization of a t(10;12)(q24;p13) in a case of CML in transformation. 940 58

Abnormalities of the short arm of chromosome 12 (12p) are found in about 5% of acute nonlymphocytic leukaemias (ANLL) and myelodysplastic syndromes (MDS). They are described to be characteristic of secondary leukaemias, especially after prior mutagenic exposure, and to be associated with a poor prognosis. In our series of 59 patients with 12p abnormalities and ANLL or MDS, exposure to genotoxic agents was proven only in five patients, but in 13/44 patients ANLL evolved from an MDS. Patients with a small deletion del(12)(p11.2p13) having a mild clinical course were distinguished from those with a large del(12)(p11.2), additional chromosomal anomalies, and a poor clinical course. Among the 31 patients with translocations or dicentric chromosomes involving 12p, a group of eight with t/dic(12;13) was the most frequent and was associated with a poor prognosis. The clinical outcome was adverse in the majority of patients with complex karyotype abnormalities, but in some patients a milder clinical course seems likely. A new, hitherto undescribed, abnormality in an MDS case with a duplication dup(12)(p11.2p13) was the amplification of the signal of the yeast artificial chromosome (YAC) clone 964c10 (D12S736). In 38 cases with deletions or unbalanced translocations/dicentrics one YAC signal was lost. Five patients with balanced translocations demonstrated breakpoints within the YAC, containing the ETV6 (TEL) gene. The breakpoints were telomeric to the YAC 964c10 in seven cases and centromeric in one patient.
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PMID:Correlation of cytogenetic, molecular cytogenetic, and clinical findings in 59 patients with ANLL or MDS and abnormalities of the short arm of chromosome 12. 950 35

Several partner genes on different chromosomes have been reported to be fused with the ETV6 gene (located in chromosome band 12p13), with different breakpoints and different frequencies, in various hematologic malignancies, particularly acute myeloid and lymphoid leukemias and myelodysplastic syndromes. By using FISH and molecular analyses, we have analyzed five different pediatric and adult patients carrying cytogenetic abnormalities involving 12p13. Our findings demonstrate that ETV6 was rearranged in all the cases analyzed. In particular, ETV6 was disrupted by translocations with chromosomal bands 7q22, 7q36, 9q11, and 13q12, not previously described as partners of ETV6 in translocations, thus extending its promiscuity in rearranging with different partner genes.
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PMID:Identification of new partner chromosomes involved in fusions with the ETV6 (TEL) gene in hematologic malignancies. 952 97


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