Therapeutic targeting of oncogenic MYB activity in T-ALL

T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that

requires treatment with intensified chemotherapy. Studies of the long-term effects of

chemotherapy in patients with T-ALL showed that recent gains in leukemia-free survival have been

achieved at the cost of significant increases in the rates of life-threatening and debilitating toxicities.

Thus, further advances in the treatment of T-ALL require the development of effective and highly

specific molecularly targeted antileukemic drugs.

The identification of cMYB translocations and duplications in human T-ALL suggests an important

oncogenic role for this transcription factor during T-cell transformation. Nevertheless, the exact

molecular mechanisms by which cMYB contributes to the pathology of this disease remains unclear.

Here, we aim to identify the role of enhanced MYB activity in enhancer driven oncogenic

transcription in the context of malignant T-cell development and investigate the in vivo role of cMyb

in the initiation and maintenance of T-ALL. Importantly, these novel insights in the pathogenic role

of cMYB in T-cell leukemia will provide new avenues for therapeutic intervention in this aggressive

human malignancy.