WEHI Masters Completion Seminar hosted by Professor Sandra Nicholson

Han Ding
Master of Research Student – Nicholson Laboratory, Immunity division, WEHI

Understanding the role of SOCS2 in immune cells and AML

Davis Auditorium

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Including Q&A session

Acute Myeloid Leukaemia (AML) is an aggressive hematological malignancy with a five-year survival rate of 30%. Activating mutations in FMS-like tyrosine kinase 3 (FLT3) occur in ~30% of AML cases, the majority of which are internal tandem duplications (FLT3-ITD). Suppressor of Cytokine Signalling 2 (SOCS2) features in several AML gene signatures, and elevated SOCS2 expression has consistently been associated with poor prognosis. Although SOCS2 has been reported to negatively regulate FLT3 and FLT3-ITD in overexpression studies, supporting evidence from in vivo models or endogenous cellular systems is lacking.

My project focused on the association between SOCS2 and FLT3 or FLT3-ITD, using in vivo and in vitro experiments alongside analysis of public AML RNA datasets. Previous work from the Nicholson lab showed that mice with a mutation in the SOCS2-SH2 domain (Socs2R96C) displayed gigantism and were indistinguishable from Socs2-/- mice (Li et al., 2022). Mice carrying FLT3-ITD develop a myeloproliferative disease (Lee et al., 2007).

During my Master’s degree, I investigated the effect of Socs2R96C on the hematopoietic differentiation and survival of Flt3ITD mice. In parallel, FLT3-ITD AML cell lines with SOCS2 overexpression or genetic deletion, were used to examine the functional relationship between SOCS2 and FLT3-ITD. Analysis of RNA data from two public AML cohorts found that SOCS2 expression was associated with FLT3-ITD and with AML primitivity, but not with FLT3. Collectively, these results indicate SOCS2 is linked to AML primitivity and FLT3-ITD expression, rather than acting as a negative regulator of FLT3-ITD signalling.

All welcome!