title: Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease.
abstract: Sustained undetectable molecular residual disease (UMRD) is obtained in a minority of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. It remains unclear whether these patients are definitively cured of their leukemia or whether leukemic stem cells (LSCs) persist in their BM. We have evaluated the presence of BCR-ABL-expressing marrow LSCs in 6 patients with chronic myeloid leukemia with sustained UMRD induced by IFN-α (n = 3), imatinib mesylate after IFN-α failure (n = 2), and dasatinib after imatinib intolerance (n = 1). Purified CD34(+) cells were used for clonogenic and long-term culture-initiating cell assays performed on classic or HOXB4-expressing MS-5 feeders. Using this strategy, we identified BCR-ABL-expressing LSCs in all patients. Interestingly, long-term culture-initiating cell assays with MS-5/HOXB4 stromal feeders increased detected numbers of LSCs in 3 patients. The relation between LSC persistency and a potential risk of disease relapse for patients with durable UMRD (on or off tyrosine kinase inhibitor therapy) warrants further investigation.
authors.affiliation: Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, Poitiers, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Chomel
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Bonnet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sorel
authors.forename: Angelina
authors.initials: A
authors.lastname: Bertrand
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Meunier
authors.forename: Serge
authors.initials: S
authors.lastname: Fichelson
authors.forename: Michael
authors.initials: M
authors.lastname: Melkus
authors.forename: Annelise
authors.initials: A
authors.lastname: Bennaceur-Griscelli
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Ali G
authors.initials: AG
authors.lastname: Turhan
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000473:pathology*; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D025202:Molecular Diagnostic Techniques / Q000592:standards / Q000706:statistics & numerical data; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D012074:Remission Induction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor