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, IL-3 starved and wild-type Ba/F3 cells were then seeded at 10

. Ghezraoui, For detection of translocation junctions from pooled cells expressing CRISPR/Cas9, we performed a nested PCR on 50 ng of genomic DNA as previously described, Genomic DNA from cells was extracted using E.Z.N.A Tissue DNA Kit (Omega Biotek), 2014.

. Ghezraoui, Briefly one-round PCR was performed on four serial dilutions of DNA from transfected cells, 2014.

, RT-PCR and cDNA amplification of fusion transcript 5 days after transfection, RNA was extracted using Nucleospin RNA Kit

, RT-PCR was performed using ProtoScript® II First Strand cDNA Synthesis Kit (NEB) according to manufacturer's instructions. Primers sequences are listed in Table S4

. Brunet, PCR product was cloned between NheI and EcoRI sites in pLJM1-EGFP plasmid (Addgene Plasmid 19319). pLJM1-NPM1-ALK vector was then transfected in RPEheating at 95°C for 10 minutes. First-round PCR was performed on lysate with primers used for translocation junction detection (listed below). Second-round PCR was performed with SYBR green in real-time PCR conditions, NPM1-ALK cDNA overexpression NPM1-ALK cDNA was amplified by PCR from SUDHLI cells using primers containing NheI and EcoRI sites, 2009.

, X-100, 0.1% SDS, 150 mM NaCl, 1 mM EDTA, and 1 mM DTT

M. Dtt-stock, Thermo Fisher Scientific). Typically, 30 µg of protein extracts were run on an 8% (w/v) Tris-HCl SDS PAGE gel. For SUDHL1 control cell line, 10 µg of protein extract were used. Gel was blotted, and probed with Phospho-ALK (Tyr1604), ALK (31F12), Phospho-STAT3 (Tyr705), Stat3, Phospho-p44/42 MAPK (ERK1/2) (Thr202/Tyr204), p44/42 MAPK (ERK1/2), Phospho-AKT (Thr308), Phospho-AKT (Ser473), and AKT antibodies from Cell Signaling. Murine NPM1-ALK protein expression was assessed with ALK (M19) antibody, with addition of Complete cocktail protease inhibitor tablets (Roche) and Halt Protease and Phosphatase Inhibitor Cocktail

, Other antibodies were used according to manufacturer's recommendations. Secondary antibodies were HRP-conjugated, and blot developed with ECL prime (GE Healthcare Life)

, Murine Alk and Npm1 genes were labeled using homemade probes from BAC RP23-100F5 and RP23-74P19. Mll and Af9 genes were labeled using homemade probes from BAC RP23-23P9 and RP23-440D4. Metaphase spreading, probe labeling, hybridization, washing and fluorescence detection were performed according to standard procedures, homemade NPM1 probe from BAC RP11-546B8