title: Therapy response correlates with ALDH activity in ALDH low-positive childhood acute lymphoblastic leukemias.
abstract: The malignant cells of childhood acute lymphoblastic leukemia (ALL) do not form a homogenous entity but a collection of differently maturated blasts. The most immature leukemia cells may be more resistant to therapy than the bulk of more differentiated blasts. We studied 42 patients with childhood ALL treated according to the ALL-BFM 2000 protocol. At diagnosis, we determined the immunophenotype and the aldehyde dehydrogenase (ALDH) activity of the leukemic cells. Additionally, we investigated the expression of CD34, CD38 and CD45 to define a population of immunophenotypically immature cells (CD34(+)/CD38(-)/CD45(-/low)). We then studied levels of minimal residual disease (MRD) after induction therapy (day 33) to determine therapy response. Including all cases (n = 42), there was no correlation between ALDH positive cells, CD34(+)/CD38(-)/CD45(-/low) cells and MRD levels. A subset of 18 ALLs displayed a more mature phenotype with low-ALDH positivity (< 1%). Analyzing this cohort, ALDH positive blasts overlapped with the CD34(+)/CD38(-)/CD45(-/low) population. The initial rate of ALDH positivity correlated with MRD levels at day 33 of therapy (r = 0.61, P < .01). We conclude that in pediatric ALL, ALDH positivity as a marker of immaturity and stemness has prognostic significance only in phenotypically mature cases when the ALDH activity is not a property of the majority of the leukemic blasts. In case of an immature ALL phenotype, ALDH activity might be an inherent characteristic of the whole leukemia and is not limited to a more immature subpopulation that could confer to resistance and increased MRD-levels during therapy.
authors.affiliation: Klinikum Chemnitz, Children's Hospital , Chemnitz , Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ahlers
authors.forename: Kai-Erik
authors.initials: KE
authors.lastname: Witte
authors.forename: C Philipp
authors.initials: CP
authors.lastname: Schwarze
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Martin
authors.initials: M
authors.lastname: Ebinger
mesh_terms: D000293:Adolescent; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology*; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D009363:Neoplasm Proteins; D000444:Aldehyde Dehydrogenase