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Case Reports
. 2022 Mar 16;3(2):521-525.
doi: 10.1002/jha2.413. eCollection 2022 May.

Acute myeloid leukemia in SRP54-mutated congenital neutropenia

Anthony Sabulski  1   2 , David D Grier  2   3 , Kasiani C Myers  1   2 , Stella M Davies  1   2 , Jeremy D Rubinstein  2   4
Affiliations
Case Reports

Acute myeloid leukemia in SRP54-mutated congenital neutropenia

Anthony Sabulski et al. EJHaem. .

Abstract

SRP54 mutations have recently been implicated in congenital neutropenia (CN) and the in-frame deletion, p.Thr117del, is the most common pathogenic mutation reported. The largest study of SRP54-mutated CN to-date followed 23 patients for a median of 15 years. No patients developed a hematologic malignancy in that study. Given the known risk of leukemia in other CNs it is crucial to know whether patients with SRP54-mutated CN have an increased risk of leukemia. We report the first case of leukemia in a patient with SRP54-mutated CN. A 15-year-old male with SRP54-mutated CN (p.Thr117del) was diagnosed with acute myeloid leukemia with myelodysplasia-related changes on a screening bone marrow evaluation. Next generation sequencing of the leukemia cells identified CSF3R and RUNX1 mutations. These mutations commonly co-exist in CN-associated malignancies and suggest leukemogenesis in SRP54-mutated CN may occur in a similar manner to other CNs. He was successfully treated with CPX-351 followed by hematopoietic cell transplant (HCT) and remains in remission at a follow-up time of 9 months. Although conclusions from this single report must be limited, this has potentially significant implications for both screening and treatment practices for these patients, including the role and timing of HCT.

Keywords: congenital neutropenia; hematopoietic cell transplant; pediatric leukemia.

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Conflict of interest statement

The authors have no conflicts or financial interests to disclose.

Figures

FIGURE 1
FIGURE 1
Neutrophil trend and diagnostic findings in a patient with SRP54‐mutated CN and acute myeloid leukemia (AML). (A) Absolute neutrophil count (ANC) trend starting at 2 years of age and up until 15 years of age when the patient was diagnosed with leukemia. (B) Flow cytometry reveals a population of myeloid blasts that express CD34, variable CD117, CD13, CD33, HLA‐DR, partial TdT, and partial myeloperoxidase. (C) Myeloid precursors from a surveillance marrow showing cytoplasmic granules and condensed granulation located in the Golgi. (D) Blasts at the time of leukemic transformation
See this image and copyright information in PMC

References

    1. Bellanné‐Chantelot C, Schmaltz‐Panneau B, Marty C, Fenneteau O, Callebaut I, Clauin S, et al. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman‐Diamond–like syndrome. Blood 2018;132(12):1318–31. 10.1182/blood-2017-12-820308 - DOI - PMC - PubMed
    1. Donadieu J, Beaupain B, Fenneteau O, Bellanné‐Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. Br J Haematol. 2017;179(4):557–74. 10.1111/bjh.14887 - DOI - PubMed
    1. Tamura T, Yagasaki H, Nakahara E, Ito M, Ueno M, Kanezawa K, et al. A Filipino infant with severe neutropenia owing to SRP54 mutations was successfully treated with ethnically mismatched cord blood transplantation from a Japanese cord blood bank. Ann Hematol. 2021;100(11):2859–60. 10.1007/s00277-021-04518-8 - DOI - PubMed
    1. Carden MA, Connelly JA, Weinzierl EP, Kobrynski LJ, Chandrakasan S. Severe congenital neutropenia associated with SRP54 mutation in 22q11.2 deletion syndrome: hematopoietic stem cell transplantation results in correction of neutropenia with adequate immune reconstitution. J Clin Immunol. 2018;38(5):546–9. 10.1007/s10875-018-0518-7 - DOI - PubMed
    1. Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, et al. Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman‐Diamond‐like features. J Clin Invest. 2017;127(11):4090–103. 10.1172/JCI92876 - DOI - PMC - PubMed

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