Abstract
Background:The current predictor of the Chronic myeloid leukemia (CML) patients’ outcome is the degree of response to targeted therapy; here we search for a biomarker predicting CML outcome before start of therapy. This study aimed to assess the impact of the CD34+/CD38- stem cells (SCs) burden in chronic myeloid leukemia (CML) on treatment response and patients’ outcomes. Methods:Our study included 65 CML patients in the chronic phase. The patients’ CD34+/CD38- stem cells were quantified using flowcytometry before and after treatment by frontline imatinib (IM) therapy. The median follow-up for all patients was 18 months. Results:CD34+/CD38- stem cells frequency at diagnosis and after therapies are correlated to known prognostic markers (blast cells count, spleen size, total White cell count, and clinical scores). After therapy, the leukemic stem cells count dropped rapidly. The pretreatment CD34+/CD38- stem cells burden predicts response to frontline therapy. In addition, high SCs frequency at diagnosis predicts poor molecular response, transformation to AML, and poor patients’ outcomes. Conclusion:The percentage of CD34+/CD38- SCs burden at diagnosis reflects the CML disease behavior and is considered a biomarker for predicting CML patients’ response to first-line Tyrosine kinase inhibitors (TKI) therapy.
Highlights
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by trilineage hyperplasia and arising at the level of a pluripotent stem cell
We addressed whether the quantification of stem cells frequency at diagnosis and after the start of therapy could predict the patient’s response to the first-line therapy and the CML patient’s outcome
Previous studies showed that the CD34+CD38- stem cells (SCs) quantification could be accurately quantified before and after the start of targeted therapy, which might have important implications for both effectiveness of different targeted therapy to eradicate CD34+CD38- SCs and the decision to therapy continuation (Chu et al, 2011)
Summary
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by trilineage hyperplasia and arising at the level of a pluripotent stem cell. Other causes of resistance are genetic amplification and expression of BCR-ABL or genetic aberration in leukemogenic signalling pathways and the remaining residual LSCs (Elias et al, 2011). The current predictor of the Chronic myeloid leukemia (CML) patients’ outcome is the degree of response to targeted therapy; here we search for a biomarker predicting CML outcome before start of therapy. This study aimed to assess the impact of the CD34+/CD38- stem cells (SCs) burden in chronic myeloid leukemia (CML) on treatment response and patients’ outcomes. The patients’ CD34+/CD38- stem cells were quantified using flowcytometry before and after treatment by frontline imatinib (IM) therapy. The pretreatment CD34+/CD38- stem cells burden predicts response to frontline therapy. Conclusion: The percentage of CD34+/CD38- SCs burden at diagnosis reflects the CML disease behavior and is considered a biomarker for predicting CML patients’ response to first-line Tyrosine kinase inhibitors (TKI) therapy
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