Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic lymphocytic leukemia

Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab

“…Similar results were also reported by Veronese et al, who did not find a correlation between Mcl-1 mRNA levels and known biologic prognostic markers of CLL. 9 Recursive partitioning analysis 14 was performed using Mcl-1 expression as a continuous variable, which revealed an optimal cutoff point of 0.85. At this cutoff, flow cytometry-negative status was significantly different between the 2 groups (P ϭ .01; Table 1).…”

“…11 Previous studies of chemotherapy have shown varied results when examining Mcl-1 as a biomarker. 8,9 For example, higher levels of Mcl-1 have been associated with failure to attain CR after chemotherapy with fludarabine and chlorambucil, 1,16 whereas a higher Mcl-1/Bax ratio (but not Mcl-1 level alone) was associated with poor response to rituximab in a small number of variably 17 The US Intergroup Phase III Trial (E2997) revealed no statistically significant association of Mcl-1 level or Mcl-1/Bax ratio with either CR or PFS, although trends toward this were observed and lower Mcl-1/Bax ratios were associated with overall response. 18 This discordance may be the result of logistic issues that prevented immediate preparation of whole-cell extracts in this large multi-institutional trial.…”

“…Mcl-1 modulation impacts response of CLL cells to various commonly used therapeutic agents, and loss of Mcl-1 is by itself sufficient to induce apoptosis in CLL cells. [5][6][7] Recent reports have also revealed a correlation between lower Mcl-1 protein 8 and mRNA levels 9 with known biologic prognostic markers and improved outcomes in patients with CLL.…”

Dysregulation of Apoptosis and Proliferation in CLL Cells

“…Increased expression of prosurvival protein Mcl-1 was detected in approximately half of CLL cases, what is thought to inhibit apoptosis and hamper the therapeutic effect of chlorambucil as well as fludarabine (Kitada et al, 1998;Pepper et al, 2008), and rituximab (Awan et al, 2009). Moreover, low expression of MCL-1 gene was correlated with prolonged overall survival in the disease (Veronese et al, 2008). Some other observations suggest that upregulated expression of Mcl-1 plays a crucial role in a protective influence of microenvironmental factors on leukemic cells (Pedersen et al, 2002).…”

N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity

“…6 Especially relevant is Mcl-1, for which elevated levels are associated with poor treatment response and high risk of CLL disease progression. 7,8 Mcl-1 reduction strategies were able to restore in vitro chemotherapic cytotoxicity. 6,9 CLL cells are sensitive to oxidative stress.…”