PMID- 37989463
OWN - NLM
STAT- Publisher
LR  - 20231202
IS  - 1388-2139 (Electronic)
IS  - 1383-5742 (Linking)
VI  - 793
DP  - 2023 Nov 19
TI  - Congenital neutropenia: From lab bench to clinic bedside and back.
PG  - 108476
LID - S1383-5742(23)00024-8 [pii]
LID - 10.1016/j.mrrev.2023.108476 [doi]
AB  - Neutropenia is a hematological condition characterized by a decrease in absolute 
      neutrophil count (ANC) in peripheral blood, typically classified in adults as 
      mild (1-1.5 x 10(9)/L), moderate (0.5-1 x 10(9)/L), or severe (< 0.5 x 10(9)/L). 
      It can be categorized into two types: congenital and acquired. Congenital severe 
      chronic neutropenia (SCN) arises from mutations in various genes, with different 
      inheritance patterns, including autosomal recessive, autosomal dominant, and 
      X-linked forms, often linked to mitochondrial diseases. The most common genetic 
      cause is alterations in the ELANE gene. Some cases exist as non-syndromic 
      neutropenia within the SCN spectrum, where genetic origins remain unidentified. 
      The clinical consequences of congenital neutropenia depend on granulocyte levels 
      and dysfunction. Infants with this condition often experience recurrent bacterial 
      infections, with approximately half facing severe infections within their first 
      six months of life. These infections commonly affect the respiratory system, 
      digestive tract, and skin, resulting in symptoms like fever, abscesses, and even 
      sepsis. The severity of these symptoms varies, and the specific organs and 
      systems affected depend on the genetic defect. Congenital neutropenia elevates 
      the risk of developing acute myeloid leukemia (AML) or myelodysplastic syndromes 
      (MDS), particularly with certain genetic variants. SCN patients may acquire CSF3R 
      and RUNX1 mutations, which can predict the development of leukemia. It is 
      important to note that high-dose granulocyte colony-stimulating factor (G-CSF) 
      treatment may have the potential to promote leukemogenesis. Treatment for 
      neutropenia involves antibiotics, drugs that boost neutrophil production, or bone 
      marrow transplants. Immediate treatment is essential due to the heightened risk 
      of severe infections. In severe congenital or cyclic neutropenia (CyN), the 
      primary therapy is G-CSF, often combined with antibiotics. The G-CSF dosage is 
      gradually increased to normalize neutrophil counts. Hematopoietic stem cell 
      transplants are considered for non-responders or those at risk of AML/MDS. In 
      cases of WHIM syndrome, CXCR4 inhibitors can be effective. Future treatments may 
      involve gene editing and the use of the diabetes drug empagliflozin to alleviate 
      neutropenia symptoms.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Dobrewa, Weronika
AU  - Dobrewa W
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      36\50 Sporna Str, 91-738 Lodz, Poland. Electronic address: 
      weronika.dobrewa@umed.lodz.pl.
FAU - Bielska, Marta
AU  - Bielska M
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      36\50 Sporna Str, 91-738 Lodz, Poland.
FAU - Babol-Pokora, Katarzyna
AU  - Babol-Pokora K
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      36\50 Sporna Str, 91-738 Lodz, Poland.
FAU - Janczar, Szymon
AU  - Janczar S
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      36\50 Sporna Str, 91-738 Lodz, Poland.
FAU - Mlynarski, Wojciech
AU  - Mlynarski W
AD  - Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, 
      36\50 Sporna Str, 91-738 Lodz, Poland. Electronic address: 
      wojciech.mlynarski@umed.lodz.pl.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20231119
PL  - Netherlands
TA  - Mutat Res Rev Mutat Res
JT  - Mutation research. Reviews in mutation research
JID - 101632211
SB  - IM
OTO - NOTNLM
OT  - Cyclic neutropenia
OT  - Leukemia
OT  - Molecular background
OT  - Pathomechanism
OT  - Severe congenital neutropenia
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/22 00:42
MHDA- 2023/11/22 00:42
CRDT- 2023/11/21 20:50
PHST- 2023/05/17 00:00 [received]
PHST- 2023/11/11 00:00 [revised]
PHST- 2023/11/12 00:00 [accepted]
PHST- 2023/11/22 00:42 [pubmed]
PHST- 2023/11/22 00:42 [medline]
PHST- 2023/11/21 20:50 [entrez]
AID - S1383-5742(23)00024-8 [pii]
AID - 10.1016/j.mrrev.2023.108476 [doi]
PST - aheadofprint
SO  - Mutat Res Rev Mutat Res. 2023 Nov 19;793:108476. doi: 
      10.1016/j.mrrev.2023.108476.