Studies of the Human c-
            <i>myb</i>
            Gene and Its Product in Human Acute Leukemias

Slamon, Dennis J.; Boone, Thomas C.; Murdock, Douglas C.; Keith, Duane E.; Press, Michael F.; Larson, Richard A.; Souza, Lawrence M.

doi:10.1126/science.3014652

Cited by 123 publications

(65 citation statements)

References 28 publications

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“…The MYB HMYB-1 cDNA was isolated as six of 21 MYB clones obtained from two human cDNA libraries, but the corresponding mRNA was not detected by Northern blot analysis. 30 The fact that the ratio of WTK-1 to WTK-2 clones was 5:1 in the present study may explain why we could not detect the protein encoded by WTK-2 by immunoblot analysis. It is possible that the mRNA corresponding to the WTK-2 clone is unstable.…”

Section: Discussioncontrasting

confidence: 51%

“…The sequence of WTK-2 diverged completely from that of MYB LMC-8 at nucleotide position 1062 (Figure 2a and c), and the downstream sequence was identical to the sequence of part of MYB HMYB-1 cDNA, which had been isolated from patients with acute myeloid leukemia. 30 The 3′ sequence of WTK-2 is 240 bp longer than that of MYB HMYB-1 . The ORF of WTK-2 closed seven amino acids downstream of the position of divergence.…”

Section: Cloning and Sequencing Of Myb Tk-6 Cdnamentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 51%

Section: Cloning and Sequencing Of Myb Tk-6 Cdnamentioning

confidence: 99%

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

et al. 1998

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“…MYB proteins have been identified in a large number of eukaryotic organisms ranging from fungi (Stober-Grässer et al, 1992;Ohi et al, 1994;TiceBaldwin et al, 1989) to plants (for review, see Martin and Paz-Ares, 1997;Jin and Martin, 1999) and to vertebrates (Gonda et al, 1985;Slamon et al, 1986;Nomura et al, 1988). While the MYB domain of c-MYB consists of three imperfect repeats (referred to as R1, R2, and R3), proteins with other numbers of MYB repeats have also been identified (Kranz et al, 2000;Riechmann et al, 2000;Stracke et al, 2001;Jiang et al, 2004).…”

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confidence: 99%

The Arabidopsis Transcription Factor MYB12 Is a Flavonol-Specific Regulator of Phenylpropanoid Biosynthesis

et al. 2005

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Comprehensive functional data on plant R2R3-MYB transcription factors is still scarce compared to the manifold of their occurrence. Here, we identified the Arabidopsis (Arabidopsis thaliana) R2R3-MYB transcription factor MYB12 as a flavonolspecific activator of flavonoid biosynthesis. Transient expression in Arabidopsis protoplasts revealed a high degree of functional similarity between MYB12 and the structurally closely related factor P from maize (Zea mays). Both displayed similar target gene specificity, and both activated target gene promoters only in the presence of a functional MYB recognition element. The genes encoding the flavonoid biosynthesis enzymes chalcone synthase, chalcone flavanone isomerase, flavanone 3-hydroxylase, and flavonol synthase were identified as target genes. Hence, our observations further add to the general notion of a close relationship between structure and function of R2R3-MYB factors. High-performance liquid chromatography analyses of myb12 mutant plants and MYB12 overexpression plants demonstrate a tight linkage between the expression level of functional MYB12 and the flavonol content of young seedlings. Quantitative real time reverse transcription-PCR using these mutant plants showed MYB12 to be a transcriptional regulator of CHALCONE SYNTHASE and FLAVONOL SYNTHASE in planta, the gene products of which are indispensable for the biosynthesis of flavonols.

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“…This and other information has led to the hypothesis that P92@' may be involved in the meyloid response to growth factors, possibly as a receptor for one or more CSFs. The presence of an 83 Kd c-myb-related protein (P83'"yb) has been reported in the nuclei of leukemia cells from a patient with ALL [76].…”

Section: Proteinmentioning

confidence: 99%

“…Several surveys of mRNA expression in human leukemias have been reported [62,[72][73][74][75][76][77][78][79][80][81]. These studies involve leukemia cell lines as well as fresh leukemia cells.…”

Section: Rnamentioning

confidence: 99%

Oncogenes and human leukemias

Butturini¹,

Gale

1988

The International Journal of Cell Cloning

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Abstract. Eukaryotic cells contain a family of genes termed "cellular oncogenes" or "proto-oncogenes," thought to regulate normal cell growth and development. In some circumstances, such as following transduction by retroviruses, activation of these genes causes tumors and leukemias in animals. Possible mechanisms of cellular oncogene activation include: 1) DNA point mutation, deletion or insertion, 2) gene amplification, 3) gene activation by internal rearrangement, chromosomal translocation or promoter insertion, 4) recombinative events resulting in the formation of novel chimeric genes, and others.

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Studies of the Human c- myb Gene and Its Product in Human Acute Leukemias

Cited by 123 publications

References 28 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

The Arabidopsis Transcription Factor MYB12 Is a Flavonol-Specific Regulator of Phenylpropanoid Biosynthesis

Oncogenes and human leukemias

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