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Differential antigen expression and aberrant signaling via PI3/AKT, MAP/ERK, JAK/STAT, and Wnt/ β catenin pathways in Lin−/CD38−/CD34+ cells in acute myeloid leukemia
Author(s) -
Garg Swati,
Shanmukhaiah Chandrakala,
Marathe Supreet,
Mishra Prashant,
Babu Rao Vunditi,
Ghosh Kanjaksha,
Madkaikar Manisha
Publication year - 2016
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12592
Subject(s) - myeloid leukemia , cd38 , stem cell , population , cancer research , cd34 , myeloid , biology , leukemia , protein kinase b , wnt signaling pathway , immunology , cd44 , signal transduction , medicine , cell , microbiology and biotechnology , environmental health , genetics
Acute myeloid leukemia is often called as stem cell disease that presents with treatment failure and poor disease outcome. Leukemic stem cells in acute myeloid leukemia ( AML ) are enriched in Lineage‐/ CD 38−/ CD 34+ compartment of CD 34−positive AML . Many markers important for stem cell biology have been reported for their association with leukemic stem cell population, but what remains clinically most important is a rapid identification of prognostic information. In this study, we evaluated four signal transduction pathways and thirteen markers on Lin−/ CD 38−/ CD 34+ population in AML . Expressions were compared in different AML subtypes, survival, and treatment outcome groups. We observed that markers important in homing, cell quiescence, and signal propagation such as CD 44, CD 96, CD 90, WT ‐1, CD 123 and CD 25 were most significantly differentially expressed on Lin‐/ CD 38−/ CD 34+ population in AML from their normal counterparts ( P < 0.05, Mann–Whitney). Constitutive activation of phospho ERK , AKT , and STAT 5 in these cells was associated with poor outcome. Also, an increased frequency of putative leukemic stem cell population shows negative impact on treatment outcome and overall survival, suggesting that initial evaluation of AML samples for pLSC frequency and constitutively activated signaling pathway can provide prognostic and therapeutic information at the time of diagnosis.