Genomic Profiling of Early T cell Precursor Acute Lymphoblastic Leukemia
Mentor: David Teachey
The cure rate for children with T-cell acute lymphoblastic leukemia (T-ALL) has improved. Yet, a significant percentage of children relapse. Survival for children with relapsed T-ALL is poor. Early T-cell precursor (ETP) is a subtype of T-ALL that has unique clinical and genetic features. While the cure rates for ETP ALL are similar to non-ETP T-ALL, the reason some children are not cured is different. ETP ALL is more likely to be resistant to medicines. Non-ETP T-ALL is more likely to respond to medicines and relapse. Using standard genetic testing, ETP ALL appears less similar to T-ALL and more similar to other types of leukemia, including acute myelogenous leukemia (AML) and T-myeloid mixed phenotype acute leukemia (T-MPAL). AML and T-MPAL are treated with different medicines than T-ALL. It is very possible some patients with ETP ALL would benefit from therapies used to treat AML or T-MPAL. Standard genetic testing has not been able to define why patients with ETP ALL respond to therapy differently and why the genetics of ETP ALL are more similar to AML and T-MPAL. Improved understanding of the biology of ETP ALL may identify better treatments. It also may help identify which patients with ETP ALL should be treated with T-ALL therapy and which might benefit from AML or T-MPAL therapy. Single-cell sequencing allows scientists to perform genetic testing on individual cancer cells from a patient. Standard sequencing, in contrast, misses the diversity of cancer cells in a patient. Standard sequencing also fails to identify rare populations that drive resistance to therapy. The Teachey lab has performed standard genetic sequencing on leukemic blasts from over 1000 children with T-ALL, including over 100 children with ETP ALL. With funding from the Alex’s Lemonade Stand Foundation (ALSF), his lab is currently performing single-cell sequencing (scRNAseq) on leukemia cells from children with ETP ALL. His lab has leukemia cells from children with ETP ALL who responded to chemotherapy and were cured, leukemia cells from children who responded to chemotherapy and relapsed, and leukemia cells from children who failed to respond to chemotherapy. His lab is also performing scRNAseq on leukemic cells from children with non-ETP T-ALL, AML, and T-MPAL. His lab will integrate the scRNAseq with the standard genetic sequencing on over 1000 children with T-ALL. My project will allow me to learn how to perform and analyze scRNAseq on childhood leukemia samples.
