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Deeper and faster responses are reported with the second\u2010generation TKI Nilotinib. Sustained responses may enable TKI discontinuation. However, even in a complete molecular response, some patients experience disease recurrence possibly due to persistence of quiescent leukemic CD34+\/lin\u2212Ph+ stem cells (LSCs). Degree and mechanisms of LSCs clearance during TKI treatment are not clearly established. The PhilosoPhi34 study was designed to verify the in\u2010vivo activity and timecourse of first\u2010line Nilotinib therapy on BM CD34+\/lin\u2212Ph+ cells clearance. Eighty\u2010seven CP\u2010CML patients were enrolled. BM cells were collected and tested for Ph+ residual cells, at diagnosis, 3, 6 and 12\u00a0months of treatment. FISH analysis of unstimulated CD34+\/lin\u2212 cells in CCyR patients were positive in 8\/65 (12.3%), 5\/71 (7%), 0\/69 (0%) evaluable tests, respectively. Per\u2010Protocol analysis response rates were as follows: CCyR 95% at 12 months, MR4.5 31% and 46% at 12 and 36\u00a0months, respectively. An exploratory Gene Expression Profiling (GEP) study of CD34+\/lin\u2212 cells was performed on 30 patients at diagnosis and after, on 79 patients at diagnosis vs 12\u00a0months of nilotinib treatment vs 10 healthy subjects. Data demonstrated some genes significantly different expressed: NFKBIA, many cell cycle genes, ABC transporters, JAK\u2010STAT signaling pathway (JAK2). In addition, a correlation between different expression of some genes (JAK2, OLFM4, ICAM1, NFKBIA) among patients at diagnosis and their achievement of an early and deeper MR was observed.<\/jats:p>","DOI":"10.1111\/ejh.13680","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T17:28:15Z","timestamp":1623950895000},"page":"436-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nilotinib\u2010induced bone marrow CD34+\/lin\u2010Ph+ cells early clearance in newly diagnosed CP\u2010Chronic Myeloid Leukemia: Final report of the PhilosoPhi34 study"],"prefix":"10.1111","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-6616","authenticated-orcid":false,"given":"Ester","family":"Pungolino","sequence":"first","affiliation":[{"name":"Division of Hematology ASST Grande Ospedale Metropolitano Niguarda Milano 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