Expression of the retinoblastoma gene in human high grade non-Hodgkin's lymphomas

Weide, Rudolf; Tiemann, Markus; Pflüger, K. H.; Köppler, H.; Parviz, Behnoush; Hh, Wacker; Havemann, K.; Parwaresch,

doi:10.1016/0959-8049(93)91580-e

Cited by 18 publications

(24 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While some studies have suggested that a considerable fraction of NHL cases do not express pRB, [22][23][24][25] other studies, [27][28][29] and the present study, report that pRB is expressed in the large majority of malignant lymphomas (65 of 66 cases in our study). Consistent with previous studies, 26,27 there was a large variation in expression (Ͼ20-fold).…”

Section: Discussionsupporting

confidence: 42%

“…The discrepancies may be explained by different grading and staining methods. Martinez et al 22 and Weide et al 23 reported a reduction or loss of pRB expression by immunohistochemistry (IHC) in a large proportion of lymphomas. Kornblau et al 24 described reduced or no pRB expression in more than 30% of chronic lymphocytic leukemia (CLL) samples.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Proliferation-dependent expression and phosphorylation of pRB in B cell non-Hodgkin's lymphomas: dependence on RB1 copy number

et al. 2002

View full text Add to dashboard Cite

Some studies have suggested that a significant fraction of nonHodgkin's lymphomas (NHL) do not express pRB protein, possibly due to deletions of RB1. We examined RB1/centromere 17 copy number by fluorescent in situ hybridisation, and pRB expression/phosphorylation by immunohistochemistry (IHC) and immunoblotting (IB) in 66 cases of B cell NHL. Thirteen cases had lost one RB1 copy relative to centromere 17 copy number and total DNA content. Case 458/88 had no RB1 copies. pRB levels were heterogeneous as assessed by IB (0.04-1.12 relative units), but all tumours, except for case 458/88, expressed pRB localised to the nucleus in Ͼ75% of the tumour cells by IHC. The fraction of phosphorylated pRB was correlated with pRB expression (r 2 = 0.56, P Ͻ 0.001). The 14 cases with loss of RB1 had lower pRB expression (median 0.25) than those without (median 0.48, P Ͻ 0.001), but a correlation with S phase fraction (r 2 = 0.43, P Ͻ 0.001; previously published data for tumour-specific S phase and apoptotic fractions) indicated that the variation in pRB expression was due to differences in proliferative activity. Furthermore, the regression lines for pRB expression vs S phase fraction were not different for the cases with or without loss of one RB1 copy (P = 0.5). Cases 154/88 (one RB1 copy) and 258/88 (two RB1 copies), in addition to case 458/88, had low expression of (hypophosphorylated) pRB (0.04, 0.08 and 0.04), despite their high S phase fractions (21%, 17% and 21%). There was no association between pRB expression/RB1 copy number and apoptotic fraction. Neither pRB expression nor loss of RB1 had prognostic value, but cases 154/88, 258/88, and 458/88 had short survival times (5, 3 and 46 months, respectively) compared to the others (median survival: 44 months, P = 0.03). It is suggested that pRB expression and function are normal in 63 of 66 NHL cases, including 12 of 13 lymphomas with loss of one RB1 allele.

show abstract

Section: Discussionsupporting

confidence: 42%

Section: Introductionmentioning

confidence: 99%

Proliferation-dependent expression and phosphorylation of pRB in B cell non-Hodgkin's lymphomas: dependence on RB1 copy number

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Although the incidence of genetic alteration to the retinoblastoma gene is high in non-Hodgkin's lymphomas (NHL) (Martinez et al, 1993;Weide et al, 1994), we have identified 11 human B-cell lines which express pRb protein. This suggests that at least one allele of the retinoblastoma gene is intact in the cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…As quiescent (Go) cells enter into the cell division cycle in response to relevant extracellular signals, two changes to pRb protein become apparent: the overall level of expression increases and the protein becomes phosphorylated on multiple sites (Sinclair et al, 1994(Sinclair et al, , 1998Hollyoake et al, 1995;Kempkes et al, 1995;Szekely et al, 1995;Cannell et al 1996). Altered expression of pRb has been described in primary samples derived from high grade non-Hodgkin's lymphoma (NHL) (Martinez et al, 1993) and expression is lost in 58% of centroblastic and Burkitt's lymphomas (Weide et al, 1994).…”

mentioning

confidence: 99%

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Sinclair

Frost

1999

Br J Cancer

View full text Add to dashboard Cite

Summary Human cancers frequently sustain genetic mutations that alter the function of their G1 cell cycle control check point. These include changes to the retinoblastoma gene and to the genes that regulate its phosphorylation, such as the cyclin-dependent kinase inhibitor p16 INK4a . Altered expression of retinoblastoma protein (pRb) is associated with non-Hodgkin's lymphoma, particularly centroblastic and Burkitt's lymphomas. pRb is expressed in normal B-cells and its regulatory phosphorylation pathway is activated in response to a variety of stimuli. Since human B-lymphoma-derived cell lines are often used as in vitro model systems to analyse the downstream effects of signal transduction, we examined the functional status of pRb in a panel of human B-cell lines. We identified eleven cell lines which express the hyperphosphorylated forms of pRb. Furthermore, we suggest that the pRb protein appears to be functional in these cell lines.

show abstract

“…27 The inactivation of the Rb gene has been related to the development of aggressive NHL. 28,29 The potential role of CDKI p21 Waf1 and p27 Kip1 , and Rb in transformation of CLL has not been largely investigated. On the other hand, cyclin D1 overexpression has also been detected in a subset of atypical and clinically aggressive CLL.…”

Section: Introductionmentioning

confidence: 99%

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia

et al. 2002

View full text Add to dashboard Cite

show abstract

Expression of the retinoblastoma gene in human high grade non-Hodgkin's lymphomas

Cited by 18 publications

References 0 publications

Proliferation-dependent expression and phosphorylation of pRB in B cell non-Hodgkin's lymphomas: dependence on RB1 copy number

Proliferation-dependent expression and phosphorylation of pRB in B cell non-Hodgkin's lymphomas: dependence on RB1 copy number

Loss of functional pRB is not a ubiquitous feature of B-cell malignancies

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia

Contact Info

Product

Resources

About