Activation of Multiple Signal Transduction Pathways as a Prognostic Marker in Acute Myelogenous Leukemia
| Autor: | Lydia Campos, Amélie Duval, Emmanuelle Tavernier-Tardy, Nathalie Nadal, Denis Guyotat, Pascale Flandrin-Gresta |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | Blood. 110:2395-2395 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v110.11.2395.2395 |
| Popis: | Deregulation of signal transduction pathways (STPs) including JAK/STAT, RAS/Raf/MEK/ERK and PI3K/AKT may promote leukemogenesis by conferring cells proliferation and survival advantages in acute myelogenous leukemia (AML). The activation of these pathways had an adverse prognosis in AML and development of targeted therapies seems to be promising. Heat-shock proteins (HSP) are involved in the conformational maturation of a number of signaling proteins, and HSPs expression in AML is associated with other adverse prognostic factors (Bcl2, MRP). The aim of this work was to study STPs expression in AML, and there correlation to other adverse prognostic factors and complete remission rate. Sixty five patients with primary AML were analyzed by flow cytometry for constitutive ERK, PI3K and AKT activation, HSP90, Bcl2 and P170 expression. FAB subtypes were M0=3, M1=19, M2=16, M4=10, M5=16, M6=1. All patients received an induction treatment, 44 patients reached complete remission. Cytogenetics was available in 63 cases (Intermediate = 36, favorable = 3, unfavorable= 24). We performed a 3 color flow cytometry protocol using CD45 and CD34 to identify blast cells, and used a third antibody to the following transduction proteins (ERK, pERK, AKT, pAKT, PI3K) or intracytoplasmic proteins (Bcl2, HSP90, p170). Spontaneous growth of leukemic progenitor cells (CFU-L) was investigated in 44 samples. In AML, activated proteins were found in CD34+ cells. ERK and PI3K/AKT were frequently co-activated. Flow cytometry results showed that levels of STPs were significantly higher (p |
| Databáze: | OpenAIRE |
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