Acute lymphoblastic leukemia is a very prevalent cancer in kids and adults. Frontline radiation and chemotherapy lead to cognitive problems and can also result in secondary cancers. Additionally, about one-fourth of children and 50% of adults with acute leukemia develop resistance to therapy or relapse post therapy. Mechanisms of resistance are poorly understood and current research on oncogenesis (cancer development) mainly focuses on alterations (“mutations”) of gene units in leukemia. Our studies show that aberrant patterns of transcripts-pieces of RNA stitched together via a process called “splicing”-are critical in oncogenesis. We discovered that proteins controlling transcript stitching are aberrantly stabilized and have identified that this leads to abnormal splicing patterns. This phenomenon creates generations of transcripts not found in normal cells, that contribute to oncogenesis. HNRNPC protein is affected by this process. This protein binds RNA transcripts to control the splicing, stability, and translation of those transcripts. We show that leukemia cells depend highly on HNRNPC. We aim to further characterize mechanisms of HNRNPC regulation in leukemia, define HNRNPC functions in RNA biology and target HNRNPC using preclinical models of aggressive leukemia and a first in-class HNRNPC inhibitor. This approach is at the heart of personalized medicine, as it takes into consideration the levels of candidate proteins and our findings can translate to clinical trials