Prognostic impact of CSF3R mutations in favorable risk ...

LETTER TO BLOOD| APRIL 30, 2020

Prognostic impact of CSF3R mutations in favorable risk childhood acute myeloid leukemia

Katherine Tarlock, Todd Alonzo, Yi-Cheng Wang, Robert B. Gerbing, Rhonda E. Ries, Tiffany Hylkema, Jenny L. Smith, Julia E. Maxson, Soheil Meshinchi

Blood (2020) 135 (18): 1603–1606.

https://doi.org/10.1182/blood.2019004179

Subjects:

Clinical Trials and Observations, Myeloid Neoplasia

Topics:

ccaat/enhancer binding protein alpha, granulocyte colony-stimulating factor receptors, leukemia, myelocytic, acute, mutation, child, granulocyte colony-stimulating factor

TO THE EDITOR:

Colony-stimulating factor 3 receptor (CSF3R) is a driver of neutrophil differentiation, proliferation, and activation following granulocyte colony-stimulating factor binding, resulting in downstream signaling of tyrosine kinases, including JAK/STAT and SRC.1-3  Activating mutations in CSF3R are highly prevalent in chronic neutrophilic leukemia, but rarely identified in acute myeloid leukemia (AML).4,5  We previously reported on the identification of somatic CSF3R mutations in pediatric AML with a high degree of overlap with CEBPA mutations,6  which are associated with favorable prognosis.7  Small series have also identified CSF3R mutations among patients with the favorable risk lesions of core binding factor (CBF) AML (RUNX1-ETO fusion [t(8;21)] or CBFB-MYH11 [inv(16)/t(16;16)]).8 

In this letter, we report on the prevalence and prognostic significance of CSF3R mutations and the impact of cooperating CEBPA mutations and t(8;21) on outcome. A total of 2150...

REFERENCES

1.Lieschke GJ, Grail D, Hodgson G, et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood. 1994;84(6):1737-1746.

2.Zhu QS, Robinson LJ, Roginskaya V, Corey SJ. G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses. Blood. 2004;103(9):3305-3312.

3.Nicholson SE, Oates AC, Harpur AG, Ziemiecki A, Wilks AF, Layton JE. Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation. Proc Natl Acad Sci USA. 1994;91(8):2985-2988.

4.Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013;368(19):1781-1790.

5.Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia. 2013;27(9):1870-1873.

6.Maxson JE, Ries RE, Wang YC, et al. CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML [published correction appears in Blood. 2017;129(1):134]. Blood. 2016;127(24):3094-3098.

7.Ho PA, Alonzo TA, Gerbing RB, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group. Blood. 2009;113(26):6558-6566.

8.Zhang Y, Wang F, Chen X, et al. CSF3R mutations are frequently associated with abnormalities of RUNX1, CBFB, CEBPA, and NPM1 genes in acute myeloid leukemia. Cancer. 2018;124(16):3329-3338.

9.Bolouri H, Farrar JE, Triche T Jr., et al. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions [published correction appears in Nat Med. 2018:24(4):526]. Nat Med. 2018;24(1):103-112.

10.Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457-481.

11.Dwivedi P, Greis KD. Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies. Exp Hematol. 2017;46:9-20.

12.Sano H, Ohki K, Park MJ, et al. CSF3R and CALR mutations in paediatric myeloid disorders and the association of CSF3R mutations with translocations, including t(8; 21). Br J Haematol. 2015;170(3):391-397.

13.Su L, Tan Y, Lin H, et al. Mutational spectrum of acute myeloid leukemia patients with double CEBPA mutations based on next-generation sequencing and its prognostic significance. Oncotarget. 2018;9(38):24970-24979.

14.Su L, Gao S, Tan Y, et al. CSF3R mutations were associated with an unfavorable prognosis in patients with acute myeloid leukemia with CEBPA double mutations. Ann Hematol. 2019;98(7):1641-1646.

15.Schlenk RF, Taskesen E, van Norden Y, et al. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA. Blood. 2013;122(9):1576-1582.

16.Germeshausen M, Ballmaier M, Welte K. Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: results of a long-term survey. Blood. 2007;109(1):93-99.

17.Beekman R, Valkhof MG, Sanders MA, et al. Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. Blood. 2012;119(22):5071-5077.

18.Skokowa J, Steinemann D, Katsman-Kuipers JE, et al. Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. Blood. 2014;123(14):2229-2237.

19.Ptasinska A, Assi SA, Martinez-Soria N, et al. Identification of a dynamic core transcriptional network in t(8;21) AML that regulates differentiation block and self-renewal. Cell Rep. 2014;8(6):1974-1988.

20.Grossmann V, Bacher U, Kohlmann A, et al. Expression of CEBPA is reduced in RUNX1-mutated acute myeloid leukemia. Blood Cancer J. 2012;2(8):e86.

21.Braun TP, Okhovat M, Coblentz C, et al. Myeloid lineage enhancers drive oncogene synergy in CEBPA/CSF3R mutant acute myeloid leukemia. Nat Commun. 2019;10(1):5455.

22.Wang W, Wang X, Ward AC, Touw IP, Friedman AD. C/EBPalpha and G-CSF receptor signals cooperate to induce the myeloperoxidase and neutrophil elastase genes. Leukemia. 2001;15(5):779-786.

23.Lavallée VP, Krosl J, Lemieux S, et al. Chemo-genomic interrogation of CEBPA mutated AML reveals recurrent CSF3R mutations and subgroup sensitivity to JAK inhibitors. Blood. 2016;127(24):3054-3061.

24.Fleischman AG, Maxson JE, Luty SB, et al. The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood. 2013;122(22):3628-3631.

25.Gunawan AS, McLornan DP, Wilkins B, et al. Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia. Haematologica. 2017;102(6):e238-e240.

© 2020 by The American Society of Hematology

This program is developed by Focus Insight with the permission of American Society of Hematology, Inc. The content are excerpted from the journal Blood. Copyright © 2019 The American Society of Hematology. All rights reserved. 「American Society of Hematology」, 「ASH」 and the ASH Logo are registered trademarks of the American Society of Hematology.