Frequency and photographs of HGM11 chromosome anomalies in bone marrow samples from 3,996 patients with malignant hematologic neoplasms

Dewald, Gordon W.; Schad, Chris R.; Lilla, Virginia C.; Jalal, Syed M.

doi:10.1016/0165-4608(93)90075-w

Cited by 39 publications

(13 citation statements)

References 3 publications

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“…Although the mechanism of MDS/MPD pathogenesis remains unknown, several recurring clonal cytogenetic abnormalities are found in MDS/MPD patients. Deletion of the long arm of chromosome 20 is the most common structural abnormality in myeloid malignancies, although it is rarely seen in lymphoid neoplasms (20). Karyotypic analysis showed that 1 patient in this study diagnosed with MDS/MPDs had a deletion within 20q12 (our unpublished observations).…”

Section: Discussionmentioning

confidence: 96%

“…This is the case for chronic myelogenous leukemia, for which the BCR/ABL fusion gene allows unequivocal diagnosis and provides a likely mechanism of pathogenesis (19). Deletion of the long arm of chromosome 20 is the second most common structural abnormality in patients with hematological neoplasms (20). This anomaly is found recurrently in CMPDs, MDSs, and acute myeloblastic leukemia (AML) patients but is rarely seen in lymphoid malignancies (21,22); it is also described in some MDS/MPD patients and patients with CMPDs in transition to MDSs (10,21,23).…”

Section: Introductionmentioning

confidence: 99%

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Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

Fütterer

Campanero²,

Leonardo³

et al. 2005

J. Clin. Invest.

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The myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that share characteristics with chronic myeloproliferative diseases and myelodysplastic syndromes. The broad spectrum of clinical manifestations makes MDS/MPDs extremely difficult to diagnose and treat, with a median survival time of 1-5 years. No single gene defect has been firmly associated with MDS/MPDs, and no animal models have been developed for these diseases. The association of deletions on chromosome 20q with myeloid malignancies suggests the presence of unidentified tumor suppressor genes in this region. Here we show that the recently identified death inducer-obliterator (Dido) gene gives rise to at least 3 polypeptides (Dido1, Dido2, and Dido3) through alternative splicing, and we map the human gene to the long arm of chromosome 20. We found that targeting of murine Dido caused a transplantable disease whose symptoms and signs suggested MDS/MPDs. Furthermore, 100% of human MDS/MPD patients analyzed showed Dido expression abnormalities, which we also found in other myeloid but not lymphoid neoplasms or in healthy donors. Our findings suggest that Dido might be one of the tumor suppressor genes at chromosome 20q and that the Dido-targeted mouse may be a suitable model for studying MDS/MPD diseases and testing new approaches to their diagnosis and treatment.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

Fütterer

Campanero²,

Leonardo³

et al. 2005

J. Clin. Invest.

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“…Such deletions are believed to harbour tumour suppressor genes, loss or inactivation of which contributes to the pathogenesis of the tumour. In a large study of patients with haematological malignancies, Dewald et al (1993) analysed almost 3000 consecutive bone marrow samples with a sole chromosomal abnormality. A deletion of the long arm of chromosome 20 was found in 5% of these samples and represented the second most common structural abnormality after the Philadelphia chromosome.…”

Section: Introductionmentioning

confidence: 99%

Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes

et al. 2000

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“…T he l3mbtl1 gene is located on the long arm of chromosome 20q, within a region on 20q12 commonly deleted in several myeloid malignancies, including myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia (1). It has been proposed that the 20q12 locus contains one or more tumor suppressors, which when lost contribute to the development of these disorders.…”

Section: H4k20me1/2 Binding Protein | Chromatin Readermentioning

confidence: 99%

L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability

Gurvich¹,

Perna²,

Farina

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The l3mbtl1 gene is located on the long arm of chromosome 20 (q12), within a region commonly deleted in several myeloid malignancies. L3MBTL1 is a human homolog of the Drosophila polycomb L(3)MBT tumor suppressor protein and thus a candidate tumor suppressor in del(20q12) myeloid disorders. We used the loss-of-function approach to explore the possible tumor suppressive mechanism of L3MBTL1 and found that depletion of L3MBTL1 from human cells causes replicative stress, DNA breaks, activation of the DNA damage response, and genomic instability. L3MBTL1 interacts with Cdc45, MCM2-7 and PCNA, components of the DNA replication machinery, and is required for normal replication fork progression, suggesting that L3MBTL1 causes DNA damage, at least in part, by perturbing DNA replication. An activated DNA damage response and genomic instability are common features in tumorigenesis and a consequence of overexpression of many oncogenes. We propose that the loss of L3MBTL1 contributes to the development of 20q − hematopoietic malignancies by inducing replicative stress, DNA damage, and genomic instability. T he l3mbtl1 gene is located on the long arm of chromosome 20q, within a region on 20q12 commonly deleted in several myeloid malignancies, including myeloproliferative neoplasms, myelodysplastic syndromes, and acute myeloid leukemia (1). It has been proposed that the 20q12 locus contains one or more tumor suppressors, which when lost contribute to the development of these disorders. L3MBTL1 is a human homolog of the Drosophila polycomb group (PcG) protein L(3)MBT. Homozygous mutations of the Drosophila l3mbt gene cause malignant transformation of the adult optic neuroblasts and ganglion mother cells in the larval brain (2). Somatic, focal deletions of other human L3MBTL family members, the l3mbtl2 and l3mbtl3 genes, have recently been found in human medulloblastoma (3). These findings suggest that L3MBTL1 is a candidate tumor suppressor gene in myeloid malignancies associated with 20q12 deletions.The L3MBTL1 protein contains three MBT repeats, which assume a three-bladed propeller-like architecture, as well as a Zn finger and an SPM dimerization domain (4, 5). We previously demonstrated that L3MBTL1 functions as an HDAC-independent transcriptional repressor (6) that binds preferentially to mono-and dimethylated lysines of histones via the second of its three MBT repeats (7,8). The three MBT domains of L3MBTL1 are sufficient to compact nucleosomal arrays. This compaction requires that the nucleosome contain a mono-or dimethylated lysine 26 on histone H1b or lysine 20 on histone H4 (H4K20) (7). L3MBTL1 binds to chromatin most prominently during the S phase of the cell cycle, concomitant with the appearance of the monomethylated H4K20 (H4K20me1) mark (8), suggesting that the biological function of L3MBTL1 may be related to DNA replication.The accurate duplication of DNA during replication is essential for maintaining genomic stability, as uncorrected errors made during this process can lead to DNA breaks, which generate mutat...

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Frequency and photographs of HGM11 chromosome anomalies in bone marrow samples from 3,996 patients with malignant hematologic neoplasms

Cited by 39 publications

References 3 publications

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms

Chromosome 20 deletions in myeloid malignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes

L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability

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