myb oncogene in human hematopoietic neoplasia with 6q− anomaly

Ohyashiki, Kazuma; Ohyashiki, Junko H.; Kinniburgh, Alan J.; Toyama, Keisuke; Ito, Hisao; Minowada, Jun; Sandberg, Avery A.

doi:10.1016/0165-4608(88)90053-2

Cited by 13 publications

(3 citation statements)

References 34 publications

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“…[11][12][13][14][15][16][17]33 In this paper we examined the TK-6 cell line, which had been established in our laboratory from a patient with CML in T cell blast crisis, 18 for c-MYB gene abnormality. We found that TK-6 expresses c-MYB mRNA of a different size (2.0 kb) at a high level.…”

Section: Discussionmentioning

confidence: 99%

Truncated c-Myb expression in the human leukemia cell line TK-6

et al. 1998

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The c-MYB proto-oncogene encodes a transcription factor which plays an important role in hematopoiesis. We detected truncated c-MYB mRNA (2.0 kb) and c-Myb protein (55 kDa) in the TK-6 cell line, which was established from a patient with chronic myelogenous leukemia in T cell blast crisis. Mutated c-MYB cDNA clone (WTK-1) was isolated from a TK-6 cell cDNA library and sequenced in its entirety. Compared with the wildtype human c-MYB sequence, the WTK-1 sequence diverged at the 3′ ends of exons 9. A termination codon was present as the second codon downstream from the point of divergence and was followed by a previously unknown rearranged sequence. The conceptual protein encoded by WTK-1 (Myb TK-6 ) comprises 402 amino acids and lacks the negative regulatory domain of the normal c-Myb, reminiscent of the activated form of Myb protein. Luciferase reporter assay in NIH3T3 cells showed that the expression vector encoding Myb TK-6 stimulated Myb-regulated mim-1 promoter more effectively than that encoding wild-type human c-Myb, suggesting that Myb TK-6 is functional as a transcription factor, and thus as a potential transforming protein. Southern blot and mutant allele-specific polymerase chain reaction analyses showed that the same rearrangement of the c-MYB gene in TK-6 was present in late, but not in early, specimens obtained from the patient, indicating that this mutation had been acquired during disease progression.

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Section: Discussionmentioning

confidence: 99%

Truncated c-Myb expression in the human leukemia cell line TK-6

et al. 1998

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“…It has been argued, however, that the high MYB expression might be related to the lineage of the neoplasms rather than to the chromosome 6 abnormality (Ohyashiki et al, 1988;Hirata et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor Loci

Johansson

Mertens

Mitelman

1993

Genes Chromosomes & Cancer

167

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Research in oncogenetics has led to the identification of two major classes of tumor-associated genes, oncogenes and tumor suppressor genes. In a wide variety of solid tumor types, mutations of both groups of genes have been implicated in the tumorigenic process. In hematologic neoplasms, on the other hand, most attention has focused on illegitimate activation of oncogenes, e.g., deregulation leading to disturbed transcriptional activity and structural rearrangements resulting in hybrid genes. Whether loss or mutational inactivation of tumor suppressor genes also plays an essential role in the genesis of tumors of the hematopoietic system has received less attention. Because such inactivation can be the result of karyotypically detectable loss of chromosomal material, cytogenetic studies may prove helpful in pinpointing genomic sites that harbor tumor suppressor genes. The present study is based on a total of 12,473 cytogenetically abnormal hematologic neoplasms reported in the literature to date. Among these, we selected the 6,422 cases with sole clonal chromosomal abnormalities in order to include only aberrations of importance in the genesis, rather than in the progression, of these neoplasms. All tumors with monosomies or structural abnormalities resulting in loss of chromosomal material were compiled, and for every such structural aberration, i.e., deletion, unbalanced translocation, isochromosome, and ring chromosome, the chromosome bands lost were ascertained. This cytogenetic deletion mapping revealed that the most commonly lost chromosomes were Y and 7 in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloproliferative disorders (MPD); X, Y, 7, 20, and 21 in acute lymphocytic leukemia (ALL); X, Y, and 17 in chronic lymphoproliferative disorders (LPD); and X and Y in non-Hodgkin's lymphoma (NHL). Chromosome segments/bands lost due to unbalanced structural abnormalities in at least 5% of the cases were 5q13-33, 7q22-36, 9q13-31, 11q23-25, 12p12-13, 17p11-13, and 20q11-13 in AML; 5q13-35 and 20q11-13 in MDS; 5q22-23, 7q22, 13q12-22, 17p11-13, and 20q11-13 in MPD; 6q15-27, 9p11-24, 12p12-13, and 19p13 in ALL; 6q16-27, 11q21-25, 13q13-14, and 14q32 in LPD; and 6q21-27, 11q13-25, and 14q24-32 in NHL. Based on these findings, three conclusions can be drawn. First, there is no good correspondence between total and partial monosomies, the only exception being -7 and 7q-, both of which are common in myeloid neoplasms. This indicates different pathogenetic effects of total and partial losses.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Overexpression of the c-MYB gene has been reported most frequently in human hematopoietic malignancies. Barletta et al and others (125, 126) found that deletions of the long arm of chromosome 6 (6q-), was frequently found in acute lymphoblastic leukemias (ALLs), non-Hodgkin lymphomas, and myeloid leukemias with high levels of c-MYB expression although the c-MYB locus was not allelic. The c-MYB gene was retained on 6q22, which was bordered by chromosomal breakpoints in both interstitial and terminal 6q- deletions.…”

Section: Overexpression Of C-myb In Human Cancermentioning

confidence: 99%

c-MYB and DMTF1 in Cancer

Fry

Inoue

2019

Cancer Investigation

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The c-Myb gene encodes a transcription factor that regulates cell proliferation, differentiation, and apoptosis through protein-protein interaction and transcriptional regulation of signaling pathways. The protein is frequently overexpressed in human leukemias, breast cancers, and other solid tumors suggesting that it is a bona fide oncogene. c-MYB is often overexpressed by translocation in human tumors with t(6;7)(q23;q34) resulting in c-MYB-TCRβ in T cell ALL, t(X;6)(p11;q23) with c-MYB-GATA1 in acute basophilic leukemia, and t(6;9)(q22–23;p23–24) with c-MYB-NF1B in adenoid cystic carcinoma. Antisense oligonucleotides to c-MYB were developed to purge bone marrow cells to eliminate tumor cells in leukemias. Recently small molecules that inhibit c-MYB activity have been developed to disrupt its interaction with p300. The Dmp1 (cyclin D binding myb-like protein 1; Dmtf1) gene was isolated through its virtue for binding to cyclin D2. It is a transcription factor that has a Myb-like repeat for DNA binding. The Dmtf1 protein directly binds to the Arf promoter for transactivation and physically interacts with p53 to activate the p53 pathway. The gene is hemizygously deleted in 35–42% of human cancers, and is associated with longer survival. The significances of aberrant expression of c-MYB and DMTF1 proteins in human cancers and their clinical significances are discussed.

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myb oncogene in human hematopoietic neoplasia with 6q− anomaly

Cited by 13 publications

References 34 publications

Truncated c-Myb expression in the human leukemia cell line TK-6

Truncated c-Myb expression in the human leukemia cell line TK-6

Cytogenetic deletion maps of hematologic neoplasms: Circumstantial evidence for tumor suppressor Loci

c-MYB and DMTF1 in Cancer

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