Academic Journal
S885 IN SEARCH OF THE RESIDUAL LEUKAEMIC CLONE IN CHRONIC MYELOID LEUKAEMIA PATIENTS IN TREATMENT‐FREE REMISSION
| العنوان: | S885 IN SEARCH OF THE RESIDUAL LEUKAEMIC CLONE IN CHRONIC MYELOID LEUKAEMIA PATIENTS IN TREATMENT‐FREE REMISSION |
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| المؤلفون: | Pagani, I.S., Dang, P., Saunders, V.A., Grose, R., Shanmuganathan, N., Carne, L., Rwodzi, Z., Watts, S.M., McLean, J., Braley, J., Yeung, D.T., Branford, S., Yong, A., White, D.L., Hughes, T.P., Ross, D.M. |
| المصدر: | HemaSphere ; volume 3, issue S1, page 398 ; ISSN 2572-9241 2572-9241 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2019 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Background: Approximately half of the patients with chronic myeloid leukaemia (CML) who stop tyrosine kinase inhibitors (TKIs) after a stable deep molecular response (DMR) remain in treatment free remission (TFR), while the remaining patients need to re‐start TKI therapy. In an updated report of the TWISTER study we demonstrated the persistence of BCR‐ABL1 ‐positive cells with falling levels of residual disease, detected by highly‐sensitive patient‐specific genomic DNA PCR. The characteristics of the leukemic cells that remain after successful TKI treatment are not known. Understanding which cells persist despite TKI therapy could inform strategies aimed at recruiting more patients to TFR. Aims: To determine the lineage of residual BCR‐ABL1 ‐positive cells from patients in TFR. Methods: Twenty CML patients in TFR with undetectable BCR‐ABL1 transcript (uMR 4.5 ) for 1–11 years (median 3.0 years) provided peripheral blood for fluorescence‐activated cell sorting into granulocytes (CD16+CD66+), monocytes (CD14+), B cells (CD3‐CD19+), T cells (CD19‐CD3+), and NK cells (CD3‐CD19‐CD56+). B‐cells were then separated into mature‐naïve (CD27‐IgD+) and memory cells (CD27+IgD‐ switched memory; CD27+IgD+ non‐switched memory; CD27‐IgD‐ double‐negative). DNA nested Q‐PCR was performed on sorted cells using 20 replicates of 500 ng of DNA (total 10 ug) reaching a sensitivity of MR 6.2 (one in ∼2 million cells) in the various cell fractions. Results: BCR‐ABL1 DNA was detected in total leukocytes from 14/20 TFR patients with a median value of MR 5.6 (range MR 5.1 ‐MR 6.2 ). Even when BCR‐ABL1 DNA was not detected in total leukocytes it was sometimes detected in sorted fractions (4/6), likely reflecting concentration of measurable residual disease (MRD) in the relevant population. BCR‐ABL1 DNA was detected in B cells (n = 18 patients), T cells (n = 11), NK cells (n = 5) and monocytes (n = 4). Notably, BCR‐ABL1 was not detected in T cells if the B cell fraction was negative and BCR‐ABL1 values were consistently higher in B cells ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1097/01.hs9.0000561820.12198.70 |
| DOI: | 10.1097/01.HS9.0000561820.12198.70 |
| الاتاحة: | http://dx.doi.org/10.1097/01.hs9.0000561820.12198.70 https://onlinelibrary.wiley.com/doi/pdf/10.1097/01.HS9.0000561820.12198.70 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.F64E257C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1097/01.hs9.0000561820.12198.70 |
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