Levels of retinoblastoma protein expression in newly diagnosed acute myelogenous leukemia

Abstract

The relationship between the level of retinoblastoma protein (RB) expression and the survival of 113 newly diagnosed acute myelogenous leukemia (AML) patients was studied. Western blotting was used to determine the level of RB protein present in peripheral blood leukemia cells and results were confirmed in 26 patients by immunohistochemistry. The leukemic cells from 22/113 AML patients (19%) contained RB protein at levels that were equal to or less than the level of RB observed in the mononuclear cell fraction of peripheral blood from normal individuals (Low RB). Levels of RB greater than that of normal blood (Elevated RB) were seen in 91 patients (81%). The median survival of patients with low RB was significantly shorter than that seen in patients with elevated RB, 12 weeks versus 40 weeks (P = .02). Remission induction frequency was 36% in low RB patients compared with 68% in AML patients with elevated RB (P = .01). Multivariate analysis showed that low RB protein level was an independent prognostic factor predictive or poor survival after allowing for other known prognostic factors. These data suggest that a low level of the RB protein at the time of diagnosis is associated with shortened survival in AML patients because of inferior response to conventional therapy. Monitoring of the RB level could identify a subgroup of AML patients with an extremely poor prognosis when treated with chemotherapy alone, who would be eligible for alternative therapeutic strategies.

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

“…Despite the lack of gene rearrangements detected in the DNA analysis, Western blotting studies showed that a significant proportion of AML patients had abnormalities of pRB. 20/86 AML patients screened (23%) had no detectable pRB ( Fig 5, lanes i, j), which is consistent with previously reported studies (Tang et al, 1990;Kornblau et al, 1994b;Zhu et al, 1994). Significant protein degradation was unlikely, because the samples had intact actin and tubulin bands.…”

“…23). This is in agreement with the study from Kornblau et al (1994b) but contrasts with the data from Tang et al (1992) who found a preponderance of pRB inactivation in the monocytic leukaemias.…”

“…2). If patients with absent or reduced pRB expression were pooled (as performed by Kornblau et al, 1994b), the CR rate was 63% compared to 70% in the others, which was again not significant (P 0 . 2).…”

“…At the protein level, the data on inactivation of pRB in AML appears to be more consistent. In one series it was shown to occur in 5/18 (28%) patients (Tang et al, 1992) and in another in 30% (Kornblau et al, 1994b). In a study of the monocytic leukaemias, 11/20 patients (55%) were found to have altered expression of pRB (Weide et al, 1993).…”

“…In a study of the monocytic leukaemias, 11/20 patients (55%) were found to have altered expression of pRB (Weide et al, 1993). Importantly, Kornblau et al (1994b) also reported that patients with reduced expression of pRB had a poorer prognosis compared with those with normal pRB.…”