title: VLA-4 and CXCR4 expression levels show contrasting prognostic impact (favorable and unfavorable, respectively) in acute myeloid leukemia.
abstract: Very late antigen-4 (VLA-4) and CXC chemokine receptor 4 (CXCR4) perform critical roles in the adhesion of hematopoietic and leukemic stem cells to marrow stromal cells. This mechanism is associated with chemoresistance in patients with acute myeloid leukemia (AML). Here, we measured VLA-4 and CXCR4 expressions in leukemic myeloblasts to determine their prognostic implications. Using multicolor flow cytometry, positive VLA-4 and CXCR4 expressions were measured in leukemic myeloblasts in bone marrow aspirates that were obtained from newly diagnosed adult AML patients (n = 98). VLA-4 expression was higher in patients at favorable or intermediate cytogenetic risk than in patients at poor risk (p < 0.001 and p = 0.002, respectively), but CXCR4 expression was not significantly different. Among the 72 non-promyelocytic leukemia patients analyzed who received cytarabine + anthracycline-based induction chemotherapy, high VLA-4 expression was independently associated with a high probability of complete remission (p = 0.019) and superior relapse-free survival (RFS) (p < 0.001). However, high CXCR4 expression independently increased the probability of relapse (p = 0.002) and was associated with a shorter RFS (p = 0.006). When categorizing patients into three groups according to VLA-4 and CXCR4 expression levels, the group of high VLA-4 and low CXCR4 showed longer RFS (p = 0.001) and overall survival (OS) (p = 0.011) than the group of low VLA-4 or high CXCR4.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Bae
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Oh
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Lee
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.forename: Young-Uk
authors.initials: YU
authors.lastname: Cho
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Park
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: Lim
authors.forename: Eul-Ju
authors.initials: EJ
authors.lastname: Seo
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D039041:Integrin alpha4beta1 / Q000096:biosynthesis*; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: C527276:CXCR4 protein, human; D039041:Integrin alpha4beta1; D019718:Receptors, CXCR4