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. 2016 Aug;30(8):1759-63.
doi: 10.1038/leu.2016.32. Epub 2016 Feb 17.

Thrombopoietin receptor is required for the oncogenic function of CALR mutants

H Nivarthi  1 , D Chen  1 , C Cleary  1 , B Kubesova  1   2 , R Jäger  1 , E Bogner  1 , C Marty  3   4 , C Pecquet  5   6 , W Vainchenker  3   4 , S N Constantinescu  5   6 , R Kralovics  1
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Thrombopoietin receptor is required for the oncogenic function of CALR mutants

H Nivarthi et al. Leukemia. 2016 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Presence of MPL is required for Ba/F3 transformation by CALR mutants. (a) Correlation of expression values (FPKM) between Ba/F3 cells retrovirally transduced with CALR wild type (wt) and del52 mutant. Differentially expressed genes are highlighted in red. The top five differentially expressed genes are labeled. (b) qPCR analysis of c-mpl expression levels in Ba/F3 cells retrovirally transduced with CALR wt and del52 mutant. A total of 106 cells (transduced and selected with puromycin) were seeded, in triplicates, in medium with or without IL-3 (1 ng/ml). The total number of live cells was counted everyday for 1 week. (c) Growth curves of Ba/F3 cells retrovirally transduced with CALR wt and mutants, individually or with MPL, in the presence and absence of IL-3 (1 ng/ml). (d) Flow cytometric analysis of the percentage of GFP (MPL)-positive cells after transduction in the bulk culture (day 0) and after 5 days in medium with or without IL-3 (1 ng/ml). (e) Dose−response curve, to increasing concentrations of IL-3, of Ba/F3 cells retrovirally transduced with CALR wt and mutants, individually or with MPL.
Figure 2
Figure 2
Only Ba/F3-MPL cells with Calr frameshift mutations to disease-associated reading frame can grow in the absence of IL-3. (a) Amino-acid sequence of exon 9 of mouse Calr upon mutation to different reading frames. (b) Schematic representation of the experimental workflow. (c) Number of cells plated and colonies analyzed under different conditions. (d) Reading frames of the two alleles of endogenous Calr in Ba/F3 parental cells with IL-3. (e) Ba/F3-MPL cells with IL-3. (f) Ba/F3-MPL cells cultured in the absence of IL-3. Color code as in (a).
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