Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice

Original citation: J Clin Invest. 2013;123(1):335–339. doi:10.1172/JCI63193.

Citation for this corrigendum: J Clin Invest. 2016;126(1):404. doi:10.1172/JCI85325.

The genotype of the Nf1 mutant mice was incorrectly described. The correct text for Methods appears below.

Mice and treatment procedures. Mx1-Cre;Nf1^{tm1Par/tm1Tyj} (referred to as Mx1-Cre;Nf1^flox/–) and control mice (Nf1^flox/+) were generated and treated with pIpC (Sigma-Aldrich) at 3–5 days, as described previously (16).

In addition, corrected sentences describing the Nf1 mutant mice in the Introduction and Results and Discussion appear below.

To address this question, we administered 901 to Mx1-Cre;Nf1^flox/– mice with MPN.

We first assessed the pharmacodynamic properties of 901 in WT and Mx1-Cre;Nf1^flox/– (Nf1 mutant) mice that received an oral gavage dose of 5 mg/kg/d for 5 days.

We randomly assigned Mx1-Cre;Nf1^flox/– mice (n = 35) and their WT littermates (n = 38) to treatment with 901 (at a daily dose of 5 mg/kg) or control vehicle for 10 weeks or until the mice became moribund.

Progressive anemia with elevated reticulocyte counts and massive splenomegaly suggested that Mx1-Cre;Nf1^flox/– mice with MPN have ineffective erythropoiesis.

In striking contrast, profiling revealed a largely inverted ratio of early-to-late erythroblasts in Mx1-Cre;Nf1^flox/– mice, with 10-fold expansion in the percentage of cells in region II, and a reciprocal decline in the number of erythroblasts progressing to region IV (Figure 2C).

To further characterize the hematopoietic compartment in Mx1-Cre;Nf1^flox/– with MPN, we enumerated KLS (c-Kit⁺lin^–Sca-1⁺) cells and myelo-erythroid progenitor populations by flow cytometry (11, 12).

In addition, corrected sentences describing the Nf1 mutant mice in the figure legends appear below.

[Figure 1] 901 reduces myeloproliferation and enhances erythropoiesis in Mx1-Cre;Nf1^flox/– (Nf1) mice.

[Figure 2] Hematopoietic tissues from 6-month-old Mx1-Cre;Nf1^flox/– (Nf1) and WT mice treated with 901 or vehicle were analyzed at the end of the trial.

[Figure 3] 901 normalizes early myelo-erythroid populations in Mx1-Cre;Nf1^flox/– (Nf1) mice.

Finally, the online version of the supplemental data has been updated to indicate the correct genotype of Nf1 mutant mice in Supplemental Figures 2–5.

The authors regret the errors.

Footnotes

See the related article beginning on page 335.