title: Is alkaline phosphatase the smoking gun for highly refractory primitive leukemic cells?
abstract: With the aim to detect candidate malignant primitive progenitor populations, we modified an original alkaline phosphatase (ALP) stem cell detection method based on the identification of alkaline phosphatase fluorescent cells in combination with flow cytometry immunophenotyping. Over a period of one year, we have been using this technique to study its activity in patients with leukemia and lymphoma, showing that changes in the alkaline phosphatase levels can be used to detect rare populations of highly refractory malignant cells. By screening different blood cancers, we have observed that this activity is not always restricted to CD34+ leukemic cells, and can be overexpressed in CD34 negative leukemia. We have verified that this method gives accurate and reproducible measurements and our preliminary results suggest that CD34+/ALPhigh cells appear to sustain leukemogenesis over time.
authors.affiliation: Josep Carreras Leukemia Research Institute, Barcelona, Spain.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Rico
authors.affiliation: Josep Carreras Leukemia Research Institute, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Juncà
authors.affiliation: Thermo Fisher Scientific, Eugene, Oregon, USA.
authors.forename: Mike D
authors.initials: MD
authors.lastname: Ward
authors.affiliation: Thermo Fisher Scientific, Eugene, Oregon, USA.
authors.forename: Jolene
authors.initials: J
authors.lastname: Bradford
authors.affiliation: Josep Carreras Leukemia Research Institute, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Petriz
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001853:Bone Marrow / Q000201:enzymology / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002648:Child; D019008:Drug Resistance, Neoplasm; D055088:Early Detection of Cancer / Q000379:methods; D057075:Enzyme Assays / Q000295:instrumentation / Q000379:methods*; D005260:Female; D005434:Flow Cytometry / Q000295:instrumentation / Q000379:methods; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping / Q000295:instrumentation / Q000379:methods; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497422:KMT2A protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D000469:Alkaline Phosphatase
keywords: CD34; Vybrant DyeCycle Violet; alkaline phosphatase; leukemic stem cells; stem cells