Jerald P. Radich
M.D., University of California School of Medicine - Davis, 1983.
Molecular genetics of leukemia and the detection of minimal residual disease.
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.
Massively parallel digital transcriptional profiling of single cells.. Nature communications. 8:14049.. 2017.
Next Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2017.
Molecular monitoring of chronic myeloid leukemia: present and future.. Expert review of molecular diagnostics. 16(10):1083-1091.. 2016.
High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. :JCO2016690073.. 2016.
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia.. Nature communications. 7:13331.. 2016.
Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 22(11):1974-1982.. 2016.
Chronic myeloid leukemia: reminiscences and dreams.. Haematologica. 101(5):541-58.. 2016.
Management of Advanced-Phase Chronic Myelogenous Leukemia.. Journal of the National Comprehensive Cancer Network : JNCCN. 14(5 Suppl):669-71.. 2016.
CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML.. Blood. 127(24):3094-3098.. 2016.
Paper or plastic? BCR-ABL1 quantitation and mutation detection from dried blood spots. Blood. 127(22):2773-2774.. 2016.
NCCN Guidelines Insights: Chronic Myeloid Leukemia, Version 1.2017.. Journal of the National Comprehensive Cancer Network : JNCCN. 14(12):1505-1512.. 2016.
Combined Population Dynamics and Entropy Modelling Supports Patient Stratification in Chronic Myeloid Leukemia.. Scientific reports. 6:24057.. 2016.
Optical painting and fluorescence activated sorting of single adherent cells labelled with photoswitchable Pdots.. Nature communications. 7:11468.. 2016.
Sequencing small genomic targets with high efficiency and extreme accuracy.. Nature methods. 12(5):423-5.. 2015.
Treatment milestones in chronic myelogenous leukemia: stay the course or change therapy? Journal of the National Comprehensive Cancer Network : JNCCN. 13(5 Suppl):697-9.. 2015.
Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission? Journal of clinical oncology : official journal of the American Society of Clinical Oncology.. 2015.
Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 33(10):1157-64.. 2015.
Single-cell genotyping demonstrates complex clonal diversity in acute myeloid leukemia.. Science translational medicine. 7(281):281re2.. 2015.
Chronic myelogenous leukemia, version 1.2015.. Journal of the National Comprehensive Cancer Network : JNCCN. 12(11):1590-610.. 2014.