Yazarlar : Tang M, Gonen M, Quintas-Cardama A, Cortes J, Kantarjian H, Field C, Hughes TP, Branford S, Michor F.

Yayın : Blood.

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21653938

Konu : Lösemi

Literatür İçeriği :

Abstract

Treatment of chronic myeloid leukemia (CML) with the tyrosine kinase inhibitors (TKIs) imatinib and nilotinib represents a successful application of molecularly targeted anti-cancer therapy. However, the effect of TKIs on leukemic stem cells remains incompletely understood. Based on a statistical modeling approach using the 10-year imatinib treatment response of CML patients and a patient cohort receiving first-line nilotinib therapy, we found that successful long-term therapy results in a tri-phasic exponential decline of BCR-ABL1 transcripts in many patients. Within our framework, the first slope of -0.052 ± 0.018 (imatinib) and -0.042 ± 0.015 (nilotinib) per day represents the turnover rate of leukemic differentiated cells, while the second slope of -0.0057 ± 0.0038 (imatinib) and -0.0019 ± 0.0013 (nilotinib) per day represents the turnover rate of leukemic progenitor cells. The third slope allows an inference of the behavior of immature leukemic cells, potentially stem cells. This third slope is negative in most patients, positive in others, and not observable in some patients. This variability in response may be due to insufficient follow-up, missing data, disease heterogeneity, inconsistent adherence to drug, or acquired resistance. Our approach suggests that long-term TKI therapy may reduce the abundance of leukemic stem cells in some patients.

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