Amplification of the megakaryocytic lineage in CALRdel52 and CALRins5 mice. (A) Percentage of GFP⁺ MKs (CD41⁺CD42⁺ cells) in BM and spleen in 10 months post-BMT mice (n = 3). (B) Evolution of the percentage of GFP⁺ platelets in blood (n = 20-22). Bonferroni multiple comparison test: **P < .001, ***P < .0001. (C) Frequency of BM and spleen MKs in CALRwt-, CALRdel52-, and CALRins5-transduced 10-month-old mice (n = 3). (D) Cumulative numbers in BM plus spleen of MKs from CALRwt-, CALRdel52-, and CALRins5-transduced 10-month-old mice (n = 3). (E) Percentages of BM megakaryocytic progenitor (CFU-MKs) colonies growing in the presence of SCF, IL-6, and increasing concentrations of TPO. Values were pooled for 3, 6, and 10 months post-BMT mice (n = 13-15). Results are means ± SEM. Student t test: *P < .05, **P < .001, ***P < .0001. (F) Schematic representation of the difference in clonal amplification between CALRdel52- and CALRins5-transduced mice. Both CALRdel52 and CALRins5 mutations lead to a specific amplification of MKs and platelets in transduced mice. CALRdel52 induces an earlier amplification of hematopoietic cells (HSC compartment) than the CALRins5 mutation (CFU-MK level) leading to an overall greater production of platelets than the CALRins5 mutation.