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Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual
Jean-Claude Chomel1, Marie-Laure Bonnet, Nathalie Sorel
1Service d'Hématologie et Oncologie Biologique, CHU de Poitiers, Poitiers, France.
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.
Insights
Even with undetectable molecular residual disease (UMRD), chronic myeloid leukemia patients may still have persistent leukemic stem cells (LSCs). Further research is needed to understand the risk of relapse in these cases.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Sustained undetectable molecular residual disease (UMRD) is an uncommon outcome for chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy.
- The persistence of leukemic stem cells (LSCs) in patients achieving UMRD remains a critical question regarding potential cure and relapse risk.
Purpose of the Study:
- To investigate the presence and quantity of BCR-ABL-expressing leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) patients with sustained undetectable molecular residual disease (UMRD).
Main Methods:
- Analysis of CD34(+) cells from 6 CML patients with sustained UMRD, treated with IFN-α, imatinib, or dasatinib.
- Utilizing clonogenic and long-term culture-initiating cell assays on MS-5 stromal feeders, with and without HOXB4 expression.
Main Results:
- BCR-ABL-expressing LSCs were detected in all evaluated patients with sustained UMRD.
- Enhanced detection of LSCs was observed in three patients when using MS-5/HOXB4 stromal feeders in long-term culture-initiating cell assays.
Conclusions:
- Leukemic stem cells (LSCs) persist in the bone marrow of chronic myeloid leukemia (CML) patients even after achieving sustained undetectable molecular residual disease (UMRD).
- The potential implications of persistent LSCs for disease relapse in patients with durable UMRD require further investigation.
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