title: Evaluation of residual CD34(+) Ph(+)  progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first-line nilotinib therapy.
abstract: BACKGROUND
  Compared with imatinib, nilotinib is a potent breakpoint cluster region/v-abl Abelson murine leukemia viral oncogene (bcr-abl) kinase inhibitor, and it induces higher rate and rapid complete cytogenetic response (CCyR), yet no clinical data are available regarding its efficacy against chronic myeloid leukemia (CML) stem cells. Earlier studies demonstrated that clusters of differentiation 34-positive, Philadelphia chromosome-positive (CD34(+) Ph(+) ) cells are detectable in about 45% of patients with CML, despite being on long-term imatinib therapy and having achieved sustained CCyR.
  
  
  METHODS
  CD34(+) cells from bone marrow of de novo CML patients in the chronic phase (n = 24) treated with nilotinib (median duration of therapy, 22 months) were isolated and scored for BCR-ABL by fluorescent in situ hybridization (FISH) analysis. Similar analysis was also performed in 5 de novo CML chronic phase patients who achieved CCyR within 3 months of nilotinib therapy.
  
  
  RESULTS
  FISH evaluation of a median of 100 CD34(+) nuclei per patient revealed that only 1 of 20 (5%) evaluable patients showed residual Ph(+) progenitor cells. In this patient, just 1 of 140 (0.7%) CD34(+) interphase nuclei was found to be positive for BCR-ABL. Surprisingly, no CD34(+) Ph(+) cells were found even in those 5 patients evaluated after 3 months of nilotinib treatment.
  
  
  CONCLUSIONS
  This study assessed for the first time the persistence of CD34(+) Ph(+) cells during nilotinib first-line treatment. Preliminary results showed that in patients in CCyR, even after short-term nilotinib therapy, residual leukemic progenitors are very rarely detected compared with imatinib-treated CCyR patients. It is yet to be determined if these findings will have an impact in the path to a cure of CML with tyrosine kinase inhibitors.
authors.affiliation: Department of Hematology, University of Siena, Siena, Italy. marziadefina@libero.it
authors.forename: Marzia
authors.initials: M
authors.lastname: Defina
authors.forename: Micaela
authors.initials: M
authors.lastname: Ippoliti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzetti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Abruzzese
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Rosaria
authors.initials: R
authors.lastname: Crupi
authors.forename: Mario
authors.initials: M
authors.lastname: Tiribelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Marzia
authors.initials: M
authors.lastname: Salvucci
authors.forename: Lara
authors.initials: L
authors.lastname: Aprile
authors.forename: Claudia
authors.initials: C
authors.lastname: Baratè
authors.forename: Antonella
authors.initials: A
authors.lastname: Gozzini
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Francesco
authors.initials: F
authors.lastname: Lauria
authors.forename: Monica
authors.initials: M
authors.lastname: Bocchia
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000473:pathology; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C498826:nilotinib