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.

Defina, M., Ippoliti, M., Gozzetti, A., Abruzzese, E., Castagnetti, F., Crupi, R., et al. (2012). Evaluation of residual CD34(+) Ph(+) progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first-line nilotinib therapy. CANCER, 118(21), 5265-5269 [10.1002/cncr.27506].

Evaluation of residual CD34(+) Ph(+) progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first-line nilotinib therapy.

Gozzetti A;APRILE, LARA;BOCCHIA, MONICA
2012

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.
Defina, M., Ippoliti, M., Gozzetti, A., Abruzzese, E., Castagnetti, F., Crupi, R., et al. (2012). Evaluation of residual CD34(+) Ph(+) progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first-line nilotinib therapy. CANCER, 118(21), 5265-5269 [10.1002/cncr.27506].
File in questo prodotto:
File Dimensione Formato  
Cd34+ nilotinib Cancer 2012.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 752.18 kB
Formato Adobe PDF
752.18 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/28660
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo