Page 275 - Haematologica Vol. 107 - September 2022

LETTER TO THE EDITOR AB
CD
E
F
Figure 2. STAG1 knockdown selectively perturbs acute myeloid leukemia cells. (A) STAG1 and STAG2 expression in umbilical cord blood (UCB) and STAG2 null acute myeloid leukemia (AML) 21 cells. (B) UCB and AML cells were transduced with scrambled (Scr) and STAG1 small interfing RNA (shRNA) and transplanted into sub-lethally irradiated NSG and NSG-S mice respectively. Prior to transplantation AML xenograft cells were transduced in vitro with lentiviral particles and transferred to a new plate coated with irradiated OP9M2 stroma cells. (C) Fluorescence-activated cell sorting (FACS) plots showing the chimerism of UCB grafts (humanCD45) and frequencies of Kusabira orange-positive shRNA transduced cells at NSG bone marrow 16 weeks post transplantation. (D) Frequency of hCD45 chimerism and the proportion of transduced cells were quantified for each shRNA (n=5). Kruskal-Wallis test with comparison to the scrambled control. ns: not significant. (E) Chimerism of AML grafts (human CD45) and frequencies of Kusabira orange positive shRNA expressing cells in NSG-S bone marrow, analyzed 16 weeks post transplantation. (F) Frequency of AML engraftment and the proportion of transduced cells were quantified for each shRNA (n=4). Kruskal-Wallis test with comparison to the scrambled control. *P<0.05; **P<0.01. Scr: scrambled shRNA; Sh1: STAG1 shRNA1; Sh2: STAG1 shRNA2.
Authors
Agatheeswaran Subramaniam,1 Carl Sandén,2 Larissa Moura-Castro,2 Kristijonas Žemaitis,1 Ludwig Schmiderer,1 Aurelie Baudet,1 Alexandra Bäckström,1 Elin Arvidsson,1 Simon Hultmark,1 Natsumi Miharada,1 Mattias Magnusson,1 Kajsa Paulsson,2 Thoas Fioretos2 and Jonas Larsson1
a recent study by van der Lelij et al. identified critical el- ements of STAG1 that are essential for interaction with the RAD21 protein, thereby opening up another possibility to develop selective STAG1-RAD21 interaction inhibitors.15 Our study provides a rationale for exploiting synthetic lethality to develop more specific and targeted therapies for tumors with STAG2 mutations, demonstrating a first proof-of-con- cept within the hematopoietic system.
Haematologica | 107 September 2022
2274