title: 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.
abstract: 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-/CD38-/CD34+ compartment of CD34-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-/CD38-/CD34+ 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 CD44, CD96, CD90, WT-1, CD123 and CD25 were most significantly differentially expressed on Lin-/CD38-/CD34+ population in AML from their normal counterparts (P < 0.05, Mann-Whitney). Constitutive activation of phospho ERK, AKT, and STAT5 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.
authors.affiliation: National Institute of Immunohaematology, Mumbai, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Garg
authors.affiliation: Dr. J.C. Patel Department of Hematology, KEM Hospital, Mumbai, India.
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Shanmukhaiah
authors.affiliation: Cardio Vascular and Thoracic Centre, KEM Hospital, Mumbai, India.
authors.forename: Supreet
authors.initials: S
authors.lastname: Marathe
authors.affiliation: Cardio Vascular and Thoracic Centre, KEM Hospital, Mumbai, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Mishra
authors.affiliation: National Institute of Immunohaematology, Mumbai, India.
authors.forename: Vunditi
authors.initials: V
authors.lastname: Babu Rao
authors.affiliation: National Institute of Immunohaematology, Mumbai, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: National Institute of Immunohaematology, Mumbai, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Madkaikar
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D053612:Janus Kinases / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D050791:STAT Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D051997:ADP-ribosyl Cyclase 1
keywords: AK-5; CD116; CD123; CD135; CD25; CD44; CD90; CD96; HCK; WT-1; acute myeloid leukemia; leukemic stem cell; signal transduction