title: Aberrant marker expression patterns on the CD34+CD38- stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission.
abstract: Acute myeloid leukemia (AML) is generally regarded as a stem cell disease. In CD34-positive AML, the leukemic stem cell has been recognized as CD38 negative. This CD34+CD38- population survives chemotherapy and is most probable the cause of minimal residual disease (MRD). The outgrowth of MRD causes relapse and MRD can therefore serve as a prognostic marker. The key role of leukemogenic CD34+CD38- cells led us to investigate whether they can be detected under MRD conditions. Various markers were identified to be aberrantly expressed on the CD34+CD38- population in AML and high-risk MDS samples at diagnosis, including C-type lectin-like molecule-1 and several lineage markers/marker-combinations. Fluorescent in situ hybridization analysis revealed that marker-positive cells were indeed of malignant origin. The markers were neither expressed on normal CD34+CD38- cells in steady-state bone marrow (BM) nor in BM after chemotherapy. We found that these markers were indeed expressed in part of the patients on malignant CD34+CD38- cells in complete remission, indicating the presence of malignant CD34+CD38- cells. Thus, by identifying residual malignant CD34+CD38- cells after chemotherapy, MRD detection at the stem cell level turned out to be possible. This might facilitate characterization of these chemotherapy-resistant leukemogenic cells, thereby being of help to identify new targets for therapy.
authors.affiliation: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Rhenen
authors.forename: B
authors.initials: B
authors.lastname: Moshaver
authors.forename: A
authors.initials: A
authors.lastname: Kelder
authors.forename: N
authors.initials: N
authors.lastname: Feller
authors.forename: A W M
authors.initials: AW
authors.lastname: Nieuwint
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: G J
authors.initials: GJ
authors.lastname: Schuurhuis
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D051997:ADP-ribosyl Cyclase 1