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.

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Select Langenau Lab Publications in Acute Lymphoblastic Leukemia

  • Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia. Laukkanen S, Veloso A, Yan C, Oksa L, Alpert EJ, Do D, Hyvärinen N, McCarthy K, Adhikari A, Yang Q, Iyer S, Garcia SP, Pello A, Ruokoranta T, Moisio S, Adhikari S, Yoder JA, Gallagher K, Whelton L, Allen JR, Jin AH, Loontiens S, Heinäniemi M, Kelliher M, Heckman CA, Lohi O, Langenau DM. Blood. 2022 Oct 27;140(17):1891-1906. PubMed

  • Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia. Oliveira ML, Veloso A, Garcia EG, Iyer S, Pereira C, Barreto VM, Langenau DM, Barata JT. Leukemia. 2022 Jun;36(6):1533-1540. PubMed

  • PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis. Leukemia. 2021 Mar;35(3):679-690. Garcia EG, Veloso A, Oliveira ML, Allen JR, Loontiens S, Brunson D, Do D, Yan C, Morris R, Iyer S, Garcia SP, Iftimia N, Van Loocke W, Matthijssens F, McCarthy K, Barata JT, Speleman F, Taghon T, Gutierrez A, Van Vlierberghe P, Haas W, Blackburn JS, Langenau DM. PubMed

  • Molecularly distinct models of zebrafish Myc-induced B cell leukemia. Borga C, Foster CA, Iyer S, Garcia SP, Langenau DM, Frazer JK. Leukemia. 2019; 33(2):559-562. PubMed

  • 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. PubMed

  • 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. PubMed

For a full list of Langenau Lab publications, find out more here.