Project 8 – WT1 as a biomarker to predict relapse in patients with acute leukemia and MDS.

Relapse is a major obstacle to maximizing curative potential of allogeneic HCT (aHCT) therapy for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL)) and myelodysplastic syndrome (MDS). It has been shown that relapse can be detected through longitudinal application of quantitative PCR (qPCR) measurement techniques before patients (Pts) develop symptoms and that early intervention to delay or stop relapse can improve patient outcome. However, such tests apply only to a small percentage of Pts with fusion gene transcripts and specific mutations. WT1 has been investigated as a tumor marker in a variety of studies which have shown its association with disease progression and relapse. In our pilot work, based on WT1 kinetics data in a small cohort of Pts, we have shown the striking correspondence of increasing WT1 transcript levels with future relapse and the specific time frame between molecular relapse detected by the WT1 PCR test and hematologic relapse confirmed by clinical observations. Our plan is to establish ranges of WT1 transcript levels characteristic of Pts after aHCT that do not relapse, a high threshold level that can serve as a specific biomarker for relapse with close to or 100% specificity, and a less stringent threshold level with lower specificity to identify more Pts that relapse and at earlier times. We will also define the time interval when relapse is detected molecularly by qPCR methods, and later confirmed morphologically by standard clinical methods. Our hypothesis is that many of the Pts that will ultimately relapse will have a period of minimal residual disease that may be detected by repeated elevations of WT1 not exceeding the determined WT1 threshold levels. The ultimate purpose of our study is to apply this important biomarker as part of standard diagnostic procedures for detection of relapse in the highest-risk individuals – acute leukemia and MDS Pts undergoing aHCT.

Personnel

Anna Israyelyan, Ph.D.
Postdoctoral Fellow, Division of Translational Vaccine Research

Weimin Tsai
Research Associate II, Division of Hematology/Bone Marrow Transplantation

Lia Aquino
Clinical Research Analyst, Clinical Trials Office

Leanne Streja, Ph.D.
Senior Programmer Analyst, Department of Information Sciences