mechanisms of progression and relapse in Acute Lymphoblastic LeukemiA
Acute Lymphoblastic Leukemia (ALL) is an aggressive malignancy of thymocytes that affects thousands of children and adults in the United States each year. Recent advancements in conventional chemotherapies have improved the five-year survival rate of patients with ALL. However, patients with relapse disease are largely unresponsive to additional therapy and have a poor prognosis. Utilizing zebrafish models of relapsed T- and B-ALL, we have uncovered oncogenic drivers associated with aggression, therapy resistance and relapse. These pathways are also important regulating human leukemia progression and response to therapy. Discovering novel relapse-driving oncogenic pathways will likely identify new drug targets for the treatment of a wide array of leukemia subtypes.
Select Langenau Lab Publications in Acute Lymphoblastic Leukemia
Molecularly distinct models of zebrafish Myc-induced B cell leukemia. Borga C, Foster CA, Iyer S, Garcia SP, Langenau DM, Frazer JK. Leukemia. 2018; 10.1038/s41375-018-0328-1.
Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia. Garcia EG, Iyer S, Garcia SP, Loontiens S, Sadreyev RI, Speleman F, Langenau DM. Leukemia. 2018; 32(8):1860-1865.
TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn JS, Abraham BJ, Namiki Y, Mansour M, Abdelfattah NS, Molodtsov A, Alexe G, Toiber D, de Waard M, Jain E, Boukhali M, Lion M, Bhere D, Shah K, Gutierrez A, Stegmaier K, Silverman LB, Sadreyev RI, Asara JM, Oettinger MA, Haas W, Look AT, Young RA, Mostoslavsky R, Dellaire G, Langenau DM. Cancer Discovery. 2017; 7(11):1336-1353.
Clonal evolution enhances leukemia-propagating cell frequency in T-cell acute lymphoblastic leukemia through AKT/mTORC1 pathway activation. Blackburn JS, Liu S, Wilder JL, Dobrinski KP, Lobbardi R, Moore FE, Martinez SA, Chen EY, Lee C, Langenau DM. Cancer Cell. 2014; 25(3):366-78.
For a full list of Langenau Lab publications, find out more here.