BCL-2 Expression and Prognosis in Childhood Acute Leukemia

Abstract

Bcl-2 expression and its prognostic value were evaluated in 42 children with acute leukemia. The Bcl-2 expression of the leukemic blast cells was measured quantitatively by flow cytometry and was further analyzed by the simultaneous immunostaining of Bcl-2 with the surface membrane antigens, DNA, Ki-67 antigen. All of the cases showed a consistent expression of Bcl-2 protein; virtually all leukemic lymphoblasts were Bcl-2 positive. Although the expression of Bcl-2 varied widely from 7 to 80 x 10(3) MESF units, no significant difference was found in the mean value between the patients with acute lymphoblastic leukemia and those with acute myeloblastic leukemia. In more than half of the patients with AML, intraclonal heterogeneity of Bcl-2 expression was observed. The expression of Bcl-2 showed no apparent fluctuations during the different phases of the cell cycle. However, the proportion of Bcl-2-positive and -negative cells during the cell cycle was different between ALL and AML patients. In the ALL patients, few Bcl-2-negative cells were detected only in the GI phase, whereas in the AML patients Bcl-2-negative cells were detected in the S and G2/M phases, as well as in the G1 phase. No apparent difference was found in Bcl-2 expression between the Ki-67-negative noncycling population and the Ki-67-positive cycling population. Of the clinical features of these patients, only CD34 expression in the ALL patients was associated with high levels of Bcl-2 expression. In the 28 untreated cases of ALL, high expression of Bcl-2 was not an unfavorable factor for the outcome of this disease.

Relapse in childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo

“…15,34 Furthermore, it has been shown that relapsed ALL cells are more resistant to various drugs, such as glucocorticoids, l-asparaginase, anthracyclins, and thiopurines 35 and more frequently exhibit reduced apoptosis than newly diagnosed ALL. 36 We therefore investigated the Bax-␣ and Bcl-2 levels in lymphoblasts at first presentation and relapse from patients with childhood ALL.…”

Dexamethasone-induced apoptosis in acute lymphoblastic leukemia involves differential regulation of Bcl-2 family members

“…Several studies have investigated the predictive value of the expression level of various Bcl-2 family members in ALL at diagnosis. [35][36][37][38][39][40][41][42][43][44][45] The majority of these studies indicate that steady-state levels of individual Bcl-2 family members are not optimal predictors of outcome 35,36,38,39 or ex vivo GC-sensitivity. 37,40,42 On the other hand, several studies using cell viability assays have demonstrated that ex vivo GC-sensitivity has a predictive value in relation to the short-term response to systemic GC monotherapy and to the long-term clinical outcome in response to combination chemotherapy.…”

High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML)

“…21 Several attempts have been made to correlate expression levels of resistance genes with clinical outcome of leukemia. 14,[22][23][24][25] Only a few studies have assessed the association between candidate gene expression and survival in acute myelogenous leukemia (AML), most of them with rather small patient numbers, and sometimes with conflicting results. 9,22,26,27 Therefore, the potential prognostic value of apoptosis-related genes in AML remains to be elucidated.…”

“…14,[22][23][24][25] Only a few studies have assessed the association between candidate gene expression and survival in acute myelogenous leukemia (AML), most of them with rather small patient numbers, and sometimes with conflicting results. 9,22,26,27 Therefore, the potential prognostic value of apoptosis-related genes in AML remains to be elucidated. In this retrospective analysis, we used a semi-automated highthroughput methodology to study the expression of apoptosisrelated genes (Mdm-2, Bcl-2, Bcl-x L , Bad, Bax) in 232 AML specimens and correlated expression with response to ICT and survival.…”