BEGIN:VCALENDAR VERSION:2.0 METHOD:PUBLISH PRODID:-//Telerik Inc.//Sitefinity CMS 15.2//EN BEGIN:VTIMEZONE TZID:Eastern Standard Time BEGIN:STANDARD DTSTART:20251102T020000 RRULE:FREQ=YEARLY;BYDAY=1SU;BYHOUR=2;BYMINUTE=0;BYMONTH=11 TZNAME:Eastern Standard Time TZOFFSETFROM:-0400 TZOFFSETTO:-0500 END:STANDARD BEGIN:DAYLIGHT DTSTART:20250301T020000 RRULE:FREQ=YEARLY;BYDAY=2SU;BYHOUR=2;BYMINUTE=0;BYMONTH=3 TZNAME:Eastern Daylight Time TZOFFSETFROM:-0500 TZOFFSETTO:-0400 END:DAYLIGHT END:VTIMEZONE BEGIN:VEVENT DESCRIPTION:Sarah Skuli\, PhDDecoding Therapeutic Persistence in TP53-Mutan t Acute Myeloid Leukemia: From Metabolism to the Microenvironment\nTP53-mu tant acute myeloid leukemia (AML) is among the most treatment-refractory h uman\n malignancies\, with poor responses to existing therapies and frequ ent relapse. Although\n resistance is often attributed to fixed genetic a lterations\, emerging evidence suggests that\n leukemia cells can also su rvive therapy through dynamic\, adaptive cellular states. Our work\n demo nstrates that TP53-mutant AML cells respond to treatment by activating the \n mevalonate pathway\, enhancing antioxidant capacity and mitochondrial fitness. This\n adaptive response depends on the mevalonate pathway metab olite geranylgeranyl\n pyrophosphate and its downstream signaling program s\, revealing a targetable metabolic\n vulnerability in therapy-resistant AML.\nBuilding on these findings\, our current research focuses on drug-t olerant persister cells:\n rare\, transient cell populations that survive initial therapy and may ultimately seed relapse.\n We are integrating lo ngitudinal primary patient samples collected before\, during\, and after\n treatment with single-cell and spatial multi-omic approaches to define w hen\, where\, and\n how persister states emerge. These studies extend bey ond leukemia cell-intrinsic\n mechanisms to investigate how stromal and i mmune components of the bone marrow\n microenvironment create specialized niches that support metabolic adaptation\, immune\n evasion\, and surviv al during therapy. Together\, this work seeks to shift therapeutic\n deve lopment from targeting established resistance to identifying and eliminati ng the\n cellular states and microenvironmental interactions that sustain therapeutic persistence\n before relapse occurs.\n DTEND:20260917T170000Z DTSTAMP:20260920T080841Z DTSTART:20260917T160000Z LOCATION:Ohio\,United States\,Cincinnati\,3125 Eden Ave SEQUENCE:0 SUMMARY:Vontz Center Cancer Seminar Series UID:RFCALITEM639254885210878594 X-ALT-DESC;FMTTYPE=text/html:

Sarah Skuli\, PhD
D ecoding Therapeutic Persistence in TP53-Mutant Acute Myeloid Leukemia: Fro m Metabolism to the Microenvironment\n

TP53-mutant acute myeloi d leukemia (AML) is among the most treatment-refractory human\n malignanc ies\, with poor responses to existing therapies and frequent relapse. Alth ough\n resistance is often attributed to fixed genetic alterations\, emer ging evidence suggests that\n leukemia cells can also survive therapy thr ough dynamic\, adaptive cellular states. Our work\n demonstrates that TP5 3-mutant AML cells respond to treatment by activating the\n mevalonate pa thway\, enhancing antioxidant capacity and mitochondrial fitness. This\n adaptive response depends on the mevalonate pathway metabolite geranylgera nyl\n pyrophosphate and its downstream signaling programs\, revealing a t argetable metabolic\n vulnerability in therapy-resistant AML.\n

Bui lding on these findings\, our current research focuses on drug-tolerant pe rsister cells:\n rare\, transient cell populations that survive initial t herapy and may ultimately seed relapse.\n We are integrating longitudinal primary patient samples collected before\, during\, and after\n treatmen t with single-cell and spatial multi-omic approaches to define when\, wher e\, and\n how persister states emerge. These studies extend beyond leukem ia cell-intrinsic\n mechanisms to investigate how stromal and immune comp onents of the bone marrow\n microenvironment create specialized niches th at support metabolic adaptation\, immune\n evasion\, and survival during therapy. Together\, this work seeks to shift therapeutic\n development fr om targeting established resistance to identifying and eliminating the\n cellular states and microenvironmental interactions that sustain therapeut ic persistence\n before relapse occurs.\n

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