Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
Acute myeloid leukemia (AML) is believed to arise from leukemic stem-like cells (LSC) making understanding the biological differences between LSC and normal stem cells (HSC) or common myeloid progenitors (CMP) crucial to understanding AML biology. To determine if protein expression patterns were different in LSC compared to other AML and CD34+ populations, we measured the expression of 121 proteins by Reverse Phase Protein Arrays (RPPA) in 5 purified fractions from AML marrow and blood samples: Bulk (CD3/CD19 depleted), CD34-, CD34+(CMP), CD34+CD38+ and CD34+CD38-(LSC). LSC protein expression differed markedly from Bulk (n =31 cases, 93/121 proteins) and CD34+ cells (n = 30 cases, 88/121 proteins) with 54 proteins being significantly different (31 higher, 23 lower) in LSC than in either Bulk or CD34+ cells. Sixty-seven proteins differed significantly between CD34+ and Bulk blasts (n = 69 cases). Protein expression patterns in LSC and CD34+ differed markedly from normal CD34+ cells. LSC were distinct from CD34+ and Bulk cells by principal component and by protein signaling network analysis which confirmed individual protein analysis. Potential targetable submodules in LSC included the proteins PU.1(SP1), P27, Mcl1, HIF1α, cMET, P53, Yap, and phospho-Stats 1, 5 and 6. Protein expression and activation in LSC differs markedly from other blast populations suggesting that studies of AML biology should be performed in LSC.
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Steven M
SM
Kornblau
Amina
A
Qutub
Hui
H
Yao
Heather
H
York
Yi Hua
YH
Qiu
David
D
Graber
Farhad
F
Ravandi
Jorge
J
Cortes
Michael
M
Andreeff
Nianxiang
N
Zhang
Kevin R
KR
Coombes
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D025341:Principal Component Analysis; D060066:Protein Interaction Maps; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D055815:Young Adult
D018952:Antigens, CD34; D020543:Proteome; D051997:ADP-ribosyl Cyclase 1