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Here, we integrate Raman microscopy, FT-IR imaging, and chemometrics to explore treatment-associated spectroscopic patterns linked to differential VEN response in Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). Using two BCR-ABL1-positive cell lines with intrinsic differences in VEN sensitivity (BV-173, sensitive; SD-1, resistant), we combined classical biological readouts of apoptosis with multimodal vibrational profiling to characterize global biochemical changes induced by VEN. Sensitive BV-173 cells displayed spectroscopic changes consistent with apoptotic progression, reflected in coordinated alterations in nucleic acids, proteins, and lipids. In contrast, resistant SD-1 cells exhibited a distinct treatment-associated biochemical response profile consistent with nonapoptotic adaptation. Spectroscopic fingerprints enabled differentiation between apoptotic and nonapoptotic response patterns in the cell-line models studied. Our findings demonstrate that vibrational spectroscopy, integrated with chemometrics, may provide a complementary analytical framework for exploratory characterization of treatment-associated biochemical phenotypes in leukemia.<\/jats:p>","DOI":"10.1021\/acs.analchem.5c07689","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:01:22Z","timestamp":1786730482000},"page":"23998-24011","source":"Crossref","is-referenced-by-count":0,"title":["Spectroscopic\nSignature of Apoptosis Induced by Venetoclax\nin Philadelphia-Positive Acute Lymphoblastic Leukemia"],"prefix":"10.1021","volume":"98","author":[{"given":"Marta","family":"Szewczyk","sequence":"first","affiliation":[{"name":"Medical University of Lodz , , Pomorska 251 , ,","place":["Lodz, Poland, 92-513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Dawiec","sequence":"additional","affiliation":[{"name":"Jagiellonian University , , Gronostajowa 2 , ,","place":["Krakow, Poland, 30-387"]},{"name":"Jagiellonian University , , Lojasiewicza 11 , ,","place":["Krakow, Poland, 30-348"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4585-1525","authenticated-orcid":true,"given":"Anna M.","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"Jagiellonian University , , Gronostajowa 2 , ,","place":["Krakow, Poland, 30-387"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Jakubowska","sequence":"additional","affiliation":[{"name":"Medical University of Lodz , , Pomorska 251 , ,","place":["Lodz, Poland, 92-513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Pastorczak","sequence":"additional","affiliation":[{"name":"Medical University of Lodz , , Czechoslowacka 4 , ,","place":["Lodz, Poland, 92-216"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8826-3144","authenticated-orcid":true,"given":"Ma\u0142gorzata","family":"Baran\u0301ska","sequence":"additional","affiliation":[{"name":"Jagiellonian University , , Gronostajowa 2 , ,","place":["Krakow, Poland, 30-387"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Medical University of Lodz , , Pomorska 251 , ,","place":["Lodz, Poland, 92-513"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-883X","authenticated-orcid":true,"given":"Katarzyna","family":"Majzner","sequence":"additional","affiliation":[{"name":"Jagiellonian University , , Gronostajowa 2 , ,","place":["Krakow, Poland, 30-387"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Ostrowska","sequence":"additional","affiliation":[{"name":"Medical University of Lodz , , Pomorska 251 , ,","place":["Lodz, Poland, 92-513"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"2","key":"2026083118450896000_cit1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s11899-020-00582-5","article-title":"MLL-Rearranged Acute\nLymphoblastic Leukemia","volume":"15","author":"El Chaer","year":"2020","journal-title":"Curr. 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