Prognostic value of inhibitor of apoptosis protein family expression in patients with acute myeloid leukemia

Abstract

The inhibitor of apoptosis protein (IAP) family acts as an inhibitor of apoptosis pathways. The potential prognostic value of the expression of selected IAP family members, XIAP, cIAP-1, cIAP-2 and survivin protein, was evaluated with regard to treatment response and survival of 56 newly diagnosed adult patients with acute myeloid leukemia (AML). The presence of these IAP members influenced the achievement of a complete response (CR). In addition, overall survival (OS) was influenced by low survivin expression in univariate and multivariate analysis (p = 0.014 and p = 0.013, respectively). A strong correlation was observed between members of the IAP family (XIAP and cIAP-1, XIAP and cIAP-2, cIAP-1 and cIAP-2, p < 0.001 for all comparisons), while Smac/DIABLO demonstrated an inverse correlation with XIAP, cIAP-1 and cIAP-2 (p < 0.001 for all comparisons). Further studies should be undertaken to better demonstrate the mode of action of IAP members, as well as their prognostic and therapeutic potentials.

The role of neuronal apoptosis inhibitory protein (NAIP) in acute myeloid leukemia patients

“…Various levels of IAP family member expression have been described in AML patients. Simultaneously, a high expression of 1, 2, 3, and 4 proteins has been found to be strongly correlated with CR rates 71%, 60%, 57%, and 33%, respectively [16].…”

“…Various IAP family members have been shown to influence the outcome of AML, either alone or in combination [12][13][14][15]. It has been demonstrated that overexpression of IAP family members in AML leukemic cells correlates with a low complete remission (CR) rate and shorter overall survival (OS) [16][17][18]. Especially, a high survivin protein expression is associated with shorter OS [16].…”

“…It has been demonstrated that overexpression of IAP family members in AML leukemic cells correlates with a low complete remission (CR) rate and shorter overall survival (OS) [16][17][18]. Especially, a high survivin protein expression is associated with shorter OS [16]. Studies on XIAP have shown that its overexpression was associated with a lower CR rate and worse OS as compared to the in patients with absent or low XIAP expression [17,18].…”

SMAC mimetics as potential cancer therapeutics in myeloid malignancies

“…IAPs are preferentially upregulated in malignancy and confer drug resistance, and their overexpression is correlated, in several studies, with chemo‐resistance, tumour progression, and inferior survival outcomes (Tamm et al , ; Krajewska et al , ; Schimmer et al , ). Expression of IAPs is dysregulated in not only solid tumours but also a variety of haematological myeloid malignancies, such as acute myeloid leukaemia (AML) (Pluta et al , ), myelodysplastic syndrome (MDS) (Yamamoto et al , ), and myelofibrosis (MF) (Heaton et al , ).…”

“…Activated caspase-9 then initiates the caspase cascade culminating in apoptosis. of haematological myeloid malignancies, such as acute myeloid leukaemia (AML) (Pluta et al, 2015), myelodysplastic syndrome (MDS) (Yamamoto et al, 2004), and myelofibrosis (MF) (Heaton et al, 2018).…”