THE RETINOBLASTOMA GENE (<i>RB1</i>) IN ACUTE MYELOID LEUKAEMIA: ANALYSIS OF GENE REARRANGEMENTS, PROTEIN EXPRESSION AND COMPARISON OF DISEASE OUTCOME

Jamal, Rahman; Gale, RE; Shaun, N.; Thomas, Benjamin; Wheatley, Karrie E.; Linch, DC

doi:10.1046/j.1365-2141.1996.d01-1804.x

Cited by 24 publications

(12 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of this downregulation remains unsolved, as no deletions (Jamal et al, 1996) or mutations (Barbosa et al, 1998) of the Rb gene or methylations of CpG islands in the Rb promoter (Kornblau and Qiu, 1999) could be found as a possible mechanism for its downregulation in AML. A functional inactivation of Rb can occur by maximal phosphorylation of the protein.…”

Section: Rbmentioning

confidence: 99%

Tumor suppressor genes in normal and malignant hematopoiesis

2002

View full text Add to dashboard Cite

Section: Rbmentioning

confidence: 99%

Tumor suppressor genes in normal and malignant hematopoiesis

2002

View full text Add to dashboard Cite

“…However, in certain cell types, such as those of hematopoietic origin, mutation of the retinoblastoma gene (RB) is rarely associated with cellular transformation (27)(28)(29). Furthermore, inactivation of pRB does not appear to increase the oncogenic potential of hematopoietic cells, suggesting differential sensitivity to pRB in cellular transformation among various cell types (30).…”

mentioning

confidence: 99%

Control of retinoblastoma protein-independent hematopoietic cell cycle by the pRB-related p130

Hoshikawa

Mori

Amimoto

et al. 1998

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

View full text Add to dashboard Cite

The retinoblastoma tumor suppressor protein (pRB) is a potent inhibitor of mammalian cell growth and the functional inactivation of pRB is widely presumed to be essential for progression of the cell cycle from G 1 phase. In this work, the generality of pRB-based cell cycle control in mammalian cells was addressed by conditionally expressing pRB in cytokine-dependent hematopoietic cells. We show herein that these cells are able to progress through the cell cycle in response to cytokine despite the continued presence of supraphysiological amounts of wild-type pRB or phosphorylation-resistant pRB mutants. However, their growth was strongly blocked by ectopic expression of the pRB-related pocket protein, p130. This growth inhibition required the E2F-binding pocket domain but not the cyclin-binding domain of p130. Furthermore, increased amounts of the p130-controlled E2F, termed E2F-4, potentiated the mitogenic response of the cells to cytokine and the constitutive overexpression of E2F-4 rendered the cells cytokine-independent. Our results indicate the existence of a non-pRB-based cell cycle whose operation depends primarily on the interplay between p130 and E2F-4 in certain hematopoietic cells.

show abstract

“…6,9,31 In our pRb-negative (pRb−) group, M4 or M5 FAB subtypes were significantly more frequent than in the pRb-positive (pRb+) group. High incidence of pRb inactivation in monocytic acute leukemia has been pointed out in earlier studies.…”

Section: Discussionmentioning

confidence: 84%

True

2001

Leukemia

View full text Add to dashboard Cite

Characteristics of treatment-induced cell cycle arrest are important for in vitro and in vivo sensitivity of acute myeloid leukemia (AML) cells to cytotoxic drugs. We analyzed the expression of the major G1 cell cycle regulators (p21 Cip1 , p27 Kip1 , cyclins D, cyclin E and pRb) in 41 fresh AML cell samples. The level of p27 expression was the only factor correlated with the response to chemotherapy, a high level of p27 expression being predictive of complete remission. There was a close relation between expression of pRb, cyclin D2 and FAB subtype, illustrated by the absence of both proteins in most samples having a monocytic component (M4, M5). We also assessed the expressions of pRb, cyclin E, p21 and p27 and the activity of cdk2, the major regulator of S-phase entry, after exposure to cytosine-arabinoside (AraC) and daunorubicin (DNR), and found these proteins could characterize time-and dose-dependent cellular response to each drug. We observed hyperphosphorylated pRb, increased levels of cyclin E and a high cdk2 activity, but no p21 induction, in AML cells exposed to 10 −6 M AraC. After exposure to 10 −5 M AraC, corresponding to the serum concentration reached in high-dose AraC regimens (HDAraC), a strong p21 induction was observed, associated with similarly overexpressed cyclin E and even higher cdk2 activity than after 10 −6 M AraC, while apoptosis was significantly increased. These data suggest that cdk2 activity is likely to play a role in AraC-induced apoptosis in AML cells. This mechanism may account for high efficacy of HDAraC in cells showing little sensitivity to conventional AraC doses. Leukemia (2001) 15, 559-566.

show abstract

THE RETINOBLASTOMA GENE (RB1) IN ACUTE MYELOID LEUKAEMIA: ANALYSIS OF GENE REARRANGEMENTS, PROTEIN EXPRESSION AND COMPARISON OF DISEASE OUTCOME

Cited by 24 publications

References 29 publications

Tumor suppressor genes in normal and malignant hematopoiesis

Tumor suppressor genes in normal and malignant hematopoiesis

Control of retinoblastoma protein-independent hematopoietic cell cycle by the pRB-related p130

True

Contact Info

Product

Resources

About