A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis

Mucenski, Michael L.; McLain, Kersten; Kier, Ann B.; Swerdlow, Steven H.; Schreiner, Claire M.; Miller, Tim; Pietryga, Daniel; Scott, William J.; Potter, S. Steven

doi:10.1016/0092-8674(91)90099-k

Cited by 996 publications

(755 citation statements)

References 74 publications

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“…[3][4][5] Targeted disruption of the c-MYB locus in mice resulted in neonatal death due to failure of effective fetal hematopoiesis. 6 Activated forms of c-MYB have been separated from two independent chicken leukemia viruses, avian myeloblastosis virus (AMV) and E26, both of which cause leukemia in chickens and transform hematopoietic cells in vitro. 7 The v-Myb protein of AMV is truncated both at amino (N)-and carboxyl (C)-termini of c-Myb, and it also has several point mutations.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 1998

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“…The exact nature of this role remains to be defined. It is known that c-myb regulates hematopoietic cell proliferation [3,13 ]. Indeed, regulating progression through the G ,IS gate of the cell cycle seems to be a key function of c-myb [14].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, regulating progression through the G ,IS gate of the cell cycle seems to be a key function of c-myb [14]. myb may also play a role in regulating differentiation [13,151. These facts and the data cited above encourage us to believe that targeting of c-myb will be a useful strategy.…”

Section: Discussionmentioning

confidence: 99%

Oligodeoxynucleotide&hyphen;based therapeutics for human leukemias

Gewirtz

1993

Stem Cells

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As the cell and molecular biology of hematopoietic cell development becomes known in greater detail, the roles of individual genes in regulating cell proliferation and growth also become better appreciated. Some genes appear to be of particular importance in these complex processes and are therefore potential targets for molecularly based therapeutics. The rationale for such treatment is that, if the function of critical genes can be efficiently and specifically perturbed, then the ensuing disruption might lead to preferential leukemic cell death. Several technologies for carrying out targeted gene disruption now exist. One approach, the “antisense” gene strategy, appears to be particularly well suited to the treatment of human leukemia ex vivo and perhaps in vivo as well. Herein I review the experience of my laboratory in using this approach to target the c‐myb and c‐kit proto‐oncogenes in human leukemic cells. Our results suggest that use of oligodeoxynucleotides for disrupting the function of specific genes may prove useful for both ex vivo and in vivo treatment of patients with hematopoietic malignancies.

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“…In other investigations, it was also determined that hematopoietic progenitor cells appeared to require Myb protein during speci®c stages of development, in particular when they were actively cycling (Caracciolo et al, 1990) as might be expected given the above functional description of Myb protein. Accordingly, Myb appeared to be critical for normal hematopoietic cell development, a ®nding that was largely con®rmed using the technique of homologous recombination (Mucenski et al, 1991).…”

Section: Development Of a Myb Targeted Odnmentioning

confidence: 99%

Myb targeted therapeutics for the treatment of human malignancies

Gewirtz

1999

Oncogene

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A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis

Cited by 996 publications

References 74 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

Oligodeoxynucleotide&hyphen;based therapeutics for human leukemias

Myb targeted therapeutics for the treatment of human malignancies

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