Jack Lionberger
Mentor: Irv BersteinBox: 358080
Phone: 206-667-6879
Email: jlionber@fhcrc.org
Jack Lionberger is a fourth year Oncology fellow at the Fred Hutchinson Cancer Research Center in the lab of Irwin D. Bernstein MD. He joined the Gerontology training grant in April of 2008, after two years of research on the Fred Hutchinson Cancer Research Center Medical Oncology training grant. Jack is interested in leukemia evolution in elderly patients and in the conditions by which the marrow selects hematopoietic stem cells for use or for senescence as we age.
It is clear that genetic instability increases dramatically in people over the age of 65 in terms of increased somatic mutations, aneuploidy, and rates of most malignancies. Specifically, adult leukemia has a higher incidence of complex cytogenetic abnormalities, is more difficult to treat, and has poorer overall outcomes than childhood leukemia. Interestingly, X chromosome inactivation (XCI) in the elderly blood system is increasingly altered after the 6th decade, and in more than 30% of women the bias towards one X chromosome has been shown to be nearly complete (>80% "skewed"). It is unknown if this phenomenon is directly related to leukemia evolution, but it is predicted to reflect a shift in hematopoietic stem cell usage in the elderly female.
Lionberger's current research effort is targeted at using XCI as a marker of two stem cell populations in the normal hematopoietic system of elderly females. By studying and comparing the two populations of XCI within a single individual, he seeks genetic, epigenetic or transcriptional differences to explain the advantage incurred by the dominant stem cell pool. Although controversial, recent work by another group has suggested that the majority of these cases are not clonal. An alternative explanation may be that a qualitative trait loci or an X linked genetic or epigenetic variation between the two pools confers either an advantage or disadvantage to the affected stem cell population. Furthermore, a subset of individuals may indeed be clonal which are numerically in the extreme minority. If such a patient group exists, it may provide clues to a preleukemic cohort at risk for further leukemic evolution.