Profile of Dr. Radich

[Guest guest]

Expertise and Research Interests of Dr.

Jerald P. Radich

Molecular genetics of leukemia and the detection of minimal residual disease are

his specialty. I thought you might want to know about another doctor at the

Hutch who is making a difference.

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" We are studying the molecular genetics of response, progression, and relapse in

human leukemia. These studies rely on a close interaction of our lab to clinical

research performed at the Center, as well as collaborations with large clinical

trials of the Southwest Oncology Group. Our work falls into three major

categories:

" 1.The detection of minimal residual disease. The major obstacle to curing

leukemia is relapse. Unfortunately, the conventional definition of remission is

inadequate, as many patients deemed to be in remission nonetheless eventually

relapse. Could we cure more patients if we could identify which patients

harbored minimal residual disease (MRD) and treat those patients earlier, before

frank relapse? We use highly sensitive molecular techniques, such as the

polymerase chain reaction (PCR), to identify the molecular fingerprints of

leukemia, and then detect these fingerprints during remission, testing ifMRD

indeed predicts relapse. We have previously demonstrated that the detection of

leukemia-specific fingerprints in patients with chronic myeloid leukemia (CML)

or acute lymphoblastic leukemia (ALL) was strongly associated with subsequent

relapse. Studies are ongoing to examine the clinical significance of MRD

detection in ALL, CML, and acute myeloid leukemia (AML).

" 2. Signal transduction abnormalities in leukemia. We are using AML as a model

to examine the molecular genetics of leukemogenesis, andto map the association

of specific genetic aberrations with response and outcome. We are first trying

to dissect the involvement of a number of genes in the ras signalling pathway,

as well as perturbations of tumor suppressors causing dysfunction of

theapoptotic pathway. We are especially interested in mutations of the tyrosine

kinase Flt3, which appear to be quite common in AML, and carry a poor prognosis.

" 3. Gene expression profiles of response and progression. We are using CML as a

model diseaseto study the biology of progression and response using microarray

gene expression analysis. CML has the distinct feature of beginning in a chronic

phase which invariably evolves to a highly aggressive blast crisis. The genes

involved in this stereotyped progression are unknown. We are using the newly

evolving microarray chip systems to simultaneously examine the expression

patterns of thousands of genes during the progression of CML. In addition, we

are using this technology to examine the gene expression patterns associated

with interferon response in CML. Future studies will likely include the

examination of gene expression patterns that predict response in ALL and AML. "

FYI,

Lottie Duthu