Publication Date:
2009-11-20
Description:
Abstract 2164 Poster Board II-141 Background and Aims. Little is known on the functional and genetic integrity of Ph-negative hematopoietic cells (HC) repopulating the bone marrow after successful chronic myeloid leukemia (CML) treatment, although the frequent detection of cytogenetic abnormalities (CA), reminiscent of those seen in myelodysplastic syndromes (MDS), suggests the presence of functional and genetic defects. Telomere attrition represents a useful marker of proliferative and oxidative stress and might provide useful insights to monitor the genetic integrity of the hematopoietic compartment. This approach has been used in combination with a functional study of short and long term progenitors. Patients and methods. We investigated 78 CML patients with persistent (〉12 months) complete cytogenetic remission (CCR). Median age was 64 (23-88), M/F ratio was 1.5. Median time from diagnosis and CCR were 64 months (25-915) and 39 months (12-150) respectively. Sokal score was low in 36 patients, intermediate in 28, and high in 14. Six patients were received IFN only, 45 Imatinib only, while 27 were currently on Imatinib, but received previous treatment with INF and/or chemotherapy. Complete and partial molecular responders were 35 and 28 respectively. Fifteen patients had acquired CA (del7: 4 patients, + 8: 5 patients, del5q: 2 patients, del or +Y: 2 patients, and 2 patients had other CA). Short term progenitors (CFU-GM, BFU-E CFU-Mix) and long-term culture-initiating cells (LTC-ICs)(Sutherland HJ et al Blood 1994) have been performed on 30 patients (requiring bone marrow examination for clinical purposes). Telomere length (TRF-L) analysis was performed by Southern Blotting as previously described (Ladetto M et Al, Blood 2004), both on polymorphonucleates (PMN) and on monocyte-depleted PBMC (MD-PBMC) (Rocci et al Exp Hematol 2007) to monitor both the myeloid and lymphoid compartment. Sixty four patients were assessed on repeated samples to monitor the kinetics of telomeric loss (median time 8 months, range 6-20). A control database of 109 healthy subjects has been used for comparison. Results. Ph-negative HC of CML patients were functionally impaired compared to controls, with reduced number of CFU-Mix (median 2,62 vs 4, p=0,010), CFU-GM (median 99,5 vs 181, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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