Figure 1.
Leukemic cells with JAK GOF mutations overexpress SLFN11
(A) Diagram of proposed JAKs pathway. The canonical STAT pathway is shown in left side (blue). The non-canonical AKT and ERK pathways are shown in right side (red and green).
(B) High expression of SLFN11 in AML (red) samples in the TCGA data set. Sarcomas samples are highlighted as a reference (yellow). ACC, adrenocortical carcinoma; AML, acute myeloid leukemia; SCC, squamous cell carcinoma; DLBC, diffuse large B-cell lymphoma; GBM, glioblastoma multiforme; LGG, low grade glioma; PCPG, pheochromocytoma and paraganglioma; CE, corpus endometrial; CS, carcinosarcoma; RCC, renal cell carcinoma.
(C) Leukemic cell lines with gain-of-function (GOF) mutations in TYK2/JAK1/JAK2 consistently express high SLFN11 transcripts. The GOF variants of JAKs were mined from cBioPortal. The values represent the probability of homozygous function-impacting mutation in the GDSC or CCLE data sets. SLFN11 mRNA expression was based on multi-platform microarray average log2 intensity in the GDSC, CCLE, and NCI-60 data sets. Ph, Philadelphia chromosome; †, putative GOF mutation; ∗, GDSC; ∗∗, CCLE.
(D and E) Relative SLFN11 mRNA expression of leukemic cells with GOF mutation in JAKs compared with other leukemic cells in the CCLE and GDSC data sets. SLFN11 mRNA expression were based on multi-platform microarray average log2 intensity.
(F) Activation of the JAK/TYK2 pathway detected by Western blotting. Leukemic cell lines with GOF are highlighted in red. Chronic myeloid leukemia K562 and lung adenocarcinoma A549 were used as control cells with wild-type JAKs.