Severe congenital neutropenias

Nature Reviews Disease Primers

Volumn 3, Issue , 2017, Pages

  Skokowa, Julia ^a   Dale, David C ^b   Touw, Ivo P ^c   Zeidler, Cornelia ^d   Welte, Karl ^e  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b UNIVERSITY OF WASHINGTON   (United States)

^c ERASMUS MEDICAL CENTER   (Netherlands)

^d HANNOVER MEDICAL SCHOOL   (Germany)

^e UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROTEIN; GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE COLONY STIMULATING FACTOR RECEPTOR; GRANULOCYTE COLONY STIMULATING FACTOR RECEPTOR 3; HEMATOPOIETIC LINEAGE CELL SPECIFIC PROTEIN 1; LEUKOCYTE ELASTASE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; COLONY STIMULATING FACTOR RECEPTOR; CSF3R PROTEIN, HUMAN; HAX1 PROTEIN, HUMAN; RUNX1 PROTEIN, HUMAN; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TRANSCRIPTION FACTOR RUNX1;

APOPTOSIS; ARTICLE; BONE MARROW CELL; BONE MARROW EXAMINATION; CANCER GROWTH; ENDOPLASMIC RETICULUM STRESS; GENE EXPRESSION REGULATION; GENE MUTATION; GENETIC ANALYSIS; GERMLINE MUTATION; HUMAN; IMMUNOLOGICAL PROCEDURES; INHERITANCE; LEUKEMIA; LONG TERM CARE; MOLECULAR PATHOLOGY; MORTALITY; MULTIGENIC MUTATION; NEUTROPHIL COUNT; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PHYSICAL DISEASE BY BODY FUNCTION; PREGNANCY; PREVALENCE; PRIORITY JOURNAL; QUALITY OF LIFE; REGULATORY MECHANISM; SCREENING; SEVERE CONGENITAL NEUTROPENIA; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; ACUTE MYELOID LEUKEMIA; BLOOD CELL COUNT; COMPLICATION; GENETICS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; MUTATION; MYELODYSPLASTIC SYNDROME; NEUTROPENIA;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; BLOOD CELL COUNT; CORE BINDING FACTOR ALPHA 2 SUBUNIT; GRANULOCYTE COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; LEUKEMIA, MYELOID, ACUTE; LEUKOCYTE ELASTASE; MUTATION; MYELODYSPLASTIC SYNDROMES; NEUTROPENIA; QUALITY OF LIFE; RECEPTORS, COLONY-STIMULATING FACTOR;

EID: 85020661964     PISSN: None     EISSN: 2056676X     Source Type: Journal    
DOI: 10.1038/nrdp.2017.32     Document Type: Article

References (155)

1. Welte, K., Zeidler, C. & Dale, D. C. Severe congenital neutropenia. Semin. Hematol. 43, 189-195 (2006).
2. Skokowa, J., Germeshausen, M., Zeidler, C. & Welte, K. Severe congenital neutropenia: inheritance and pathophysiology. Curr. Opin. Hematol. 14, 22-28 (2007).
3. Donadieu, J., Beaupain, B., Mahlaoui, N. & Bellanne?Chantelot, C. Epidemiology of congenital neutropenia. Hematol. Oncol. Clin. North Am. 27, 1-17 (2013).
4. Carlsson, G. et al. Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia. Br. J. Haematol. 158, 363-369 (2012).
5. Lebel, A. et al. Genetic analysis and clinical picture of severe congenital neutropenia in Israel. Pediatr. Blood Cancer 62, 103-108 (2015).
6. Grann, V. R. et al. Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean. Br. J. Haematol. 143, 288-293 (2008).
7. Denic, S. et al. Prevalence of neutropenia in children by nationality. BMC Hematol. 16, 15 (2016).
8. Chown, G. & Gelfand, A. S. Agranulocytosis. Can. Med. Assoc. J. 29, 128-134 (1933).
9. Gilman, P. A., Jackson, D. P. & Guild, H. G. Congenital agranulocytosis: prolonged survival and terminal acute leukemia. Blood 36, 576-585 (1970).
10. Souza, L. M. et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 232, 61-65 (1986). This paper describes the cloning and production of recombinant G?CSF for potential clinical use for patients with congenital neutropenia.
11. Bonilla, M. A. et al. Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N. Engl. J. Med. 320, 1574-1580 (1989). This study reports the first successful treatment of patients with congenital neutropenia with G?CSF, who achieved neutrophil counts of 1,000 cells per ?l of blood.
12. Hammond, W. P., Price, T. H., Souza, L. M. & Dale, D. C. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N. Engl. J. Med. 320, 1306-1311 (1989). This study reports the first successful treatment of patients with cyclic neutropenia with G?CSF, who achieved increases in the median neutrophil counts.
13. Welte, K. et al. Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. Blood 75, 1056-1063 (1990).
14. Dale, D. C. et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81, 2496-2502 (1993).
15. Donadieu, J., Fenneteau, O., Beaupain, B., Mahlaoui, N. & Chantelot, C. B. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J. Rare Dis. 6, 26 (2011).
16. Rosenberg, P. S. et al. Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G?CSF therapy. Br. J. Haematol. 150, 196-199 (2010).
17. Rosenberg, P. S. et al. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G?CSF therapy. Blood 107, 4628-4635 (2006).
18. Rigaud, C. et al. Natural history of Barth syndrome: a national cohort study of 22 patients. Orphanet J. Rare Dis. 8, 70 (2013).
19. Donadieu, J. et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. Haematologica 90, 45-53 (2005).
20. Horwitz, M., Benson, K. F., Person, R. E., Aprikyan, A. G. & Dale, D. C. Mutations in ELA2, encoding neutrophil elastase, define a 21?day biological clock in cyclic haematopoiesis. Nat. Genet. 23, 433-436 (1999). This is the first description of ELANE mutations as a cause for cyclic neutropenia.
21. Dale, D. C. et al. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 96, 2317-2322 (2000). This paper reports on the detection of autosomal dominant inheritance of ELANE mutations as a cause for congenital neutropenia.
22. Horwitz, M. S. et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 109, 1817-1824 (2007).
23. Makaryan, V. et al. The diversity of mutations and clinical outcomes for ELANE-Associated neutropenia. Curr. Opin. Hematol. 22, 3-11 (2015).
24. Germeshausen, M. et al. The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Hum. Mutat. 34, 905-914 (2013).
25. Newburger, P. E. et al. Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes. Pediatr. Blood Cancer 55, 314-317 (2010).
26. Boxer, L. A., Stein, S., Buckley, D., Bolyard, A. A. & Dale, D. C. Strong evidence for autosomal dominant inheritance of severe congenital neutropenia associated with ELA2 mutations. J. Pediatr. 148, 633-636 (2006).
27. Germeshausen, M., Schulze, H., Ballmaier, M., Zeidler, C. & Welte, K. Mutations in the gene encoding neutrophil elastase (ELA2) are not sufficient to cause the phenotype of congenital neutropenia. Br. J. Haematol. 115, 222-224 (2001).
28. Benson, K. F. & Horwitz, M. Possibility of somatic mosaicism of ELA2 mutation overlooked in an asymptomatic father transmitting severe congenital neutropenia to two offspring. Br. J. Haematol. 118, 923 (2002).
29. Kostmann, R. Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr. Suppl. 45 (Suppl. 105), 1-78 (1956). A seminal description of inheritance of congenital neutropenia, which led to the term Kostmann syndrome.
30. Klein, C. et al. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat. Genet. 39, 86-92 (2007). This is the first description of autosomal recessive inheritance of congenital neutropenia-causing HAX1 mutations, including in patients with so?called Kostmann syndrome.
31. Germeshausen, M. et al. Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations. Blood 111, 4954-4957 (2008).
32. Matsubara, K. et al. Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency. Haematologica 92, e123-e125 (2007).
33. Skokowa, J. et al. Interactions among HCLS1, HAX1 and LEF?1 proteins are essential for G?CSF-triggered granulopoiesis. Nat. Med. 18, 1550-1559 (2012).
34. Skokowa, J. & Welte, K. Defective G?CSFR signaling pathways in congenital neutropenia. Hematol. Oncol. Clin. North Am. 27, 75-88 (2013).
35. Boztug, K. et al. A syndrome with congenital neutropenia and mutations in G6PC3. N. Engl. J. Med. 360, 32-43 (2009).
36. Bione, S. et al. A novel X?linked gene, G4.5. is responsible for Barth syndrome. Nat. Genet. 12, 385-389 (1996).
37. Boocock, G. R. et al. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat. Genet. 33, 97-101 (2003).
38. Bohn, G. et al. A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14. Nat. Med. 13, 38-45 (2007).
39. Menasche, G. et al. Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat. Genet. 25, 173-176 (2000).
40. Marcolongo, P. et al. Structure and mutation analysis of the glycogen storage disease type 1b gene. FEBS Lett. 436, 247-250 (1998).
41. Veiga?da?Cunha, M. et al. A gene on chromosome 11q23 coding for a putative glucose-6?phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. Am. J. Hum. Genet. 63, 976-983 (1998).
42. Germeshausen, M. et al. Digenic mutations in severe congenital neutropenia. Haematologica 95, 1207-1210 (2010).
43. Klimiankou, M. et al. GM?CSF stimulates granulopoiesis in a congenital neutropenia patient with loss?of?function biallelic heterozygous CSF3R mutations. Blood 126, 1865-1867 (2015).
44. Ward, A. C. et al. Novel point mutation in the extracellular domain of the granulocyte colony-stimulating factor (G?CSF) receptor in a case of severe congenital neutropenia hyporesponsive to G?CSF treatment. J. Exp. Med. 190, 497-507 (1999).
45. Triot, A. et al. Inherited biallelic CSF3R mutations in severe congenital neutropenia. Blood 123, 3811-3817 (2014).
46. Li, F. Q. & Horwitz, M. Characterization of mutant neutrophil elastase in severe congenital neutropenia. J. Biol. Chem. 276, 14230-14241 (2001).
47. Aprikyan, A. A. et al. Cellular and molecular abnormalities in severe congenital neutropenia predisposing to leukemia. Exp. Hematol. 31, 372-381 (2003).
48. Tidwell, T. et al. Neutropenia-Associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms. Blood 123, 562-569 (2014).
49. Grenda, D. S. et al. Mutations of the ELA2 gene found in patients with severe congenital neutropenia induce the unfolded protein response and cellular apoptosis. Blood 110, 4179-4187 (2007).
50. Nanua, S. et al. Activation of the unfolded protein response is associated with impaired granulopoiesis in transgenic mice expressing mutant Elane. Blood 117, 3539-3547 (2011).
51. Kollner, I. et al. Mutations in neutrophil elastase causing congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response. Blood 108, 493-500 (2006).
52. Nustede, R. et al. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. Br. J. Haematol. 172, 219-227 (2016).
53. Skokowa, J., Fobiwe, J. P., Dan, L., Thakur, B. K. & Welte, K. Neutrophil elastase is severely down?regulated in severe congenital neutropenia independent of ELA2 or HAX1 mutations but dependent on LEF?1. Blood 114, 3044-3051 (2009).
54. Kawaguchi, H. et al. Dysregulation of transcriptions in primary granule constituents during myeloid proliferation and differentiation in patients with severe congenital neutropenia. J. Leukoc. Biol. 73, 225-234 (2003).
55. Klimenkova, O. et al. A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation. Blood 123, 1239-1249 (2014).
56. Carlsson, G. et al. Kostmann syndrome: severe congenital neutropenia associated with defective expression of Bcl?2, constitutive mitochondrial release of cytochrome c, and excessive apoptosis of myeloid progenitor cells. Blood 103, 3355-3361 (2004).
57. Cario, G. et al. Heterogeneous expression pattern of pro-And anti-Apoptotic factors in myeloid progenitor cells of patients with severe congenital neutropenia treated with granulocyte colony-stimulating factor. Br. J. Haematol. 129, 275-278 (2005).
58. Carlsson, G. et al. Survivin expression in the bone marrow of patients with severe congenital neutropenia. Leukemia 23, 622-625 (2009).
59. Boztug, K. et al. JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. Nat. Genet. 46, 1021-1027 (2014).
60. Hayee, B. et al. G6PC3 mutations are associated with a major defect of glycosylation: a novel mechanism for neutrophil dysfunction. Glycobiology 21, 914-924 (2011).
61. Bonilla, M. A. et al. Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r?metHuG-CSF) in patients with severe congenital neutropenias. Br. J. Haematol. 88, 723-730 (1994).
62. Radomska, H. S. et al. CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors. Mol. Cell. Biol. 18, 4301-4314 (1998).
63. Rosenbauer, F. & Tenen, D. G. Transcription factors in myeloid development: balancing differentiation with transformation. Nat. Rev. Immunol. 7, 105-117 (2007).
64. Skokowa, J. et al. LEF?1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia. Nat. Med. 12, 1191-1197 (2006).
65. Skokowa, J. & Welte, K. Dysregulation of myeloid-specific transcription factors in congenital neutropenia. Ann. NY Acad. Sci. 1176, 94-100 (2009).
66. Buitenhuis, M. et al. Differential regulation of granulopoiesis by the basic helix-loop-helix transcriptional inhibitors Id1 and Id2. Blood 105, 4272-4281 (2005).
67. Mempel, K., Pietsch, T., Menzel, T., Zeidler, C. & Welte, K. Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia. Blood 77, 1919-1922 (1991).
68. Kyas, U., Pietsch, T. & Welte, K. Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia. Blood 79, 1144-1147 (1992).
69. Rauprich, P., Kasper, B., Tidow, N. & Welte, K. The protein tyrosine kinase JAK2 is activated in neutrophils from patients with severe congenital neutropenia. Blood 86, 4500-4505 (1995).
70. Gupta, K. et al. Bortezomib inhibits STAT5?dependent degradation of LEF?1, inducing granulocytic differentiation in congenital neutropenia CD34+ cells. Blood 123, 2550-2561 (2014).
71. Futami, M. et al. G?CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase. Blood 118, 1077-1086 (2011).
72. Zhu, Q. S., Robinson, L. J., Roginskaya, V. & Corey, S. J. G?CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses. Blood 103, 3305-3312 (2004).
73. Tidow, N., Kasper, B. & Welte, K. SH2?containing protein tyrosine phosphatases SHP?1 and SHP?2 are dramatically increased at the protein level in neutrophils from patients with severe congenital neutropenia (Kostmann's syndrome). Exp. Hematol. 27, 1038-1045 (1999).
74. Hirai, H. et al. C/EBP? is required for 'emergency' granulopoiesis. Nat. Immunol. 7, 732-739 (2006).
75. Skokowa, J. et al. NAMPT is essential for the G?CSF-induced myeloid differentiation via a NAD+-sirtuin?1?dependent pathway. Nat. Med. 15, 151-158 (2009). This is the first description of an alternative pathway of G?CSF-induced neutrophilic granulopoiesis in congenital neutropenia via NAMPT and the C/EBPβ emergency pathway.
76. Freedman, M. H. Safety of long-term administration of granulocyte colony-stimulating factor for severe chronic neutropenia. Curr. Opin. Hematol. 4, 217-224 (1997).
77. Welte, K. & Dale, D. Pathophysiology and treatment of severe chronic neutropenia. Ann. Hematol. 72, 158-165 (1996).
78. 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 109, 93-99 (2007).
79. Ancliff, P. J., Gale, R. E., Liesner, R., Hann, I. & Linch, D. C. Long-term follow?up of granulocyte colony-stimulating factor receptor mutations in patients with severe congenital neutropenia: implications for leukaemogenesis and therapy. Br. J. Haematol. 120, 685-690 (2003).
80. Carlsson, G. et al. Neutrophil elastase and granulocyte colony-stimulating factor receptor mutation analyses and leukemia evolution in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Haematologica 91, 589-595 (2006).
81. Germeshausen, M. et al. Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropenia. Blood 97, 829-830 (2001).
82. Germeshausen, M. et al. An acquired G?CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia. Leukemia 19, 611-617 (2005).
83. [No authors listed.] The Severe Chronic Neutropenia International Registry-European branch. Severe Chronic Neutropenia www.severe-chronic-neutropenia.org (2013).
84. Klimiankou, M. et al. Two cases of cyclic neutropenia with acquired CSF3R mutations, with 1 developing AML. Blood 127, 2638-2641 (2016).
85. Dong, F. et al. Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol. Cell. Biol. 13, 7774-7781 (1993).
86. Fukunaga, R., Ishizaka-Ikeda, E. & Nagata, S. Growth and differentiation signals mediated by different regions in the cytoplasmic domain of granulocyte colony-stimulating factor receptor. Cell 74, 1079-1087 (1993).
87. Ziegler, S. F. et al. Distinct regions of the human granulocyte-colony-stimulating factor receptor cytoplasmic domain are required for proliferation and gene induction. Mol. Cell. Biol. 13, 2384-2390 (1993).
88. Palande, K., Meenhuis, A., Jevdjovic, T. & Touw, I. P. Scratching the surface: signaling and routing dynamics of the CSF3 receptor. Front. Biosci. (Landmark Ed). 18, 91-105 (2013).
89. Touw, I. P. & van de Geijn, G. J. Granulocyte colony-stimulating factor and its receptor in normal myeloid cell development, leukemia and related blood cell disorders. Front. Biosci. 12, 800-815 (2007).
90. Dong, F. et al. Mutations in the gene for the granulocyte colony-stimulating-factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia. N. Engl. J. Med. 333, 487-493 (1995). This is the first description of acquired CSF3R mutations as an initial step in leukaemogenesis.
91. Hermans, M. H. et al. Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G?CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G?CSF receptor gene. J. Exp. Med. 189, 683-692 (1999).
92. Zhu, Q. S. et al. G?CSF induced reactive oxygen species involves Lyn-?PI3?kinase-Akt and contributes to myeloid cell growth. Blood 107, 1847-1856 (2006).
93. Liu, F. et al. Csf3r mutations in mice confer a strong clonal HSC advantage via activation of Stat5. J. Clin. Invest. 118, 946-955 (2008).
94. Dong, F. et al. Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. Leukemia 11, 120-125 (1997).
95. Germeshausen, M., Skokowa, J., Ballmaier, M., Zeidler, C. & Welte, K. G?CSF receptor mutations in patients with congenital neutropenia. Curr. Opin. Hematol. 15, 332-337 (2008).
96. Tidow, N. et al. Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia. Blood 89, 2369-2375 (1997).
97. Beekman, R. et al. Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. Blood 119, 5071-5077 (2012).
98. Skokowa, J. et al. Cooperativity of RUNX1 and CSF3R mutations in severe congenital neutropenia: a unique pathway in myeloid leukemogenesis. Blood 123, 2229-2237 (2014). A seminal paper on the role of CSF3R mutations and subsequent RUNX1 mutations in leukaemogenesis in the majority of patients with congenital neutropenia.
99. Klimiankou, M., Mellor?Heineke, S., Zeidler, C., Welte, K. & Skokowa, J. Role of CSF3R mutations in the pathomechanism of congenital neutropenia and secondary acute myeloid leukemia. Ann. NY Acad. Sci. 1370, 119-125 (2016).
100. Tschan, C. A., Pilz, C., Zeidler, C., Welte, K. & Germeshausen, M. Time course of increasing numbers of mutations in the granulocyte colony-stimulating factor receptor gene in a patient with congenital neutropenia who developed leukemia. Blood 97, 1882-1884 (2001).
101. Zeidler, C. et al. Management of Kostmann syndrome in the G?CSF era. Br. J. Haematol. 109, 490-495 (2000).
102. Bux, J., Behrens, G., Jaeger, G. & Welte, K. Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases. Blood 91, 181-186 (1998).
103. Farruggia, P. et al. Autoimmune neutropenia of infancy: data from the Italian Neutropenia Registry. Am. J. Hematol. 90, E221-E222 (2015).
104. Myers, K. C. et al. Variable clinical presentation of Shwachman-Diamond syndrome: update from the North-American Shwachman-Diamond Syndrome Registry. J. Pediatr. 164, 866-870 (2014).
105. Ghemlas, I. et al. Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes. J. Med. Genet. 52, 575-584 (2015).
106. Ancliff, P. J. et al. Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia. Blood 108, 2182-2189 (2006).
107. Gauthier?Vasserot, A. et al. Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability. Am. J. Med. Genet. A 173, 62-71 (2017).
108. Boxer, L. A. et al. Is there a role for anti-neutrophil antibody testing in predicting spontaneous resolution of neutropenia in young children. Blood 126, 2211 (2015).
109. Lee, W. I. et al. Identifying patients with neutrophil elastase (ELANE) mutations from patients with a presumptive diagnosis of autoimmune neutropenia. Immunobiology 218, 828-833 (2013).
110. Zeidler, C., Germeshausen, M., Klein, C. & Welte, K. Clinical implications of ELA2-, HAX1-, and G?CSF-receptor (CSF3R) mutations in severe congenital neutropenia. Br. J. Haematol. 144, 459-467 (2008).
111. [No authors listed.] The Severe Chronic Neutropenia International Registry. Washington.edu www.depts.washington.edu/registry (1994). References 83 and 111 show websites in which the reader can obtain handbooks for patients and their families in English and other languages.
112. Elsner, J., Roesler, J., Emmendorffer, A., Lohmann-Matthes, M. L. & Welte, K. Abnormal regulation in the signal transduction in neutrophils from patients with severe congenital neutropenia: relation of impaired mobilization of cytosolic free calcium to altered chemotaxis, superoxide anion generation and F?actin content. Exp. Hematol. 21, 38-46 (1993).
113. Koch, C. et al. GM?CSF treatment is not effective in congenital neutropenia patients due to its inability to activate NAMPT signaling. Ann. Hematol. 96, 345-353 (2017).
114. Donini, M. et al. G?CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood 109, 4716-4723 (2007).
115. Karlsson, J. et al. Low plasma levels of the protein pro?LL?37 as an early indication of severe disease in patients with chronic neutropenia. Br. J. Haematol. 137, 166-169 (2007).
116. Pütsep, K., Carlsson, G., Boman, H. G. & Andersson, M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 360, 1144-1149 (2002).
117. Ye, Y. et al. The antimicrobial propeptide hCAP?18 plasma levels in neutropenia of various aetiologies: a prospective study. Sci. Rep. 5, 11685 (2015).
118. Allen, R. C., Stevens, P. R., Price, T. H., Chatta, G. S. & Dale, D. C. In vivo effects of recombinant human granulocyte colony-stimulating factor on neutrophil oxidative functions in normal human volunteers. J. Infect. Dis. 175, 1184-1192 (1997).
119. Yakisan, E. et al. High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann's syndrome). J. Pediatr. 131, 592-597 (1997).
120. Zeidler, C. et al. Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation. Blood 95, 1195-1198 (2000).
121. Fioredda, F. et al. Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation. Blood 126, 1885-1892 (2015).
122. Oshima, K. et al. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: an analysis of 18 Japanese cases. Pediatr. Transplant. 14, 657-663 (2010).
123. Ferry, C. et al. Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. Bone Marrow Transplant. 35, 45-50 (2005).
124. Zeidler, C., Nickel, A., Sykora, K. W. & Welte, K. Improved outcome of stem cell transplantation for severe chronic neutropenia with or without secondary leukemia: a long-term analysis of European data for more than 25 years by the SCNIR. Blood 122, 3347 (2013).
125. Zeidler, C. et al. Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry. Haematologica 99, 1395-1402 (2014).
126. Boxer, L. A. et al. Use of granulocyte colony-stimulating factor during pregnancy in women with chronic neutropenia. Obstet. Gynecol. 125, 197-203 (2015).
127. Jones, E., Bolyard, A. A. & Dale, D. C. Quality of life in patients receiving granulocyte colony stimulating factor for treatment of severe chronic neutropenia. JAMA 270, 1132-1133 (1993).
128. Touw, I. P. Game of clones: the genomic evolution of severe congenital neutropenia. Hematology Am. Soc. Hematol. Educ. Program 2015, 1-7 (2015).
129. Nayak, R. C. et al. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J. Clin. Invest. 125, 3103-3116 (2015).
130. Morishima, T. et al. Genetic correction of HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis. Haematologica 99, 19-27 (2014).
131. Hiramoto, T. et al. Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells. Proc. Natl Acad. Sci. USA 110, 3023-3028 (2013).
132. Morishima, T. et al. Neutrophil differentiation from human-induced pluripotent stem cells. J. Cell. Physiol. 226, 1283-1291 (2011).
133. Lachmann, N. et al. Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies. Stem Cell Rep. 4, 282-296 (2015).
134. Dale, D. C. & Welte, K. Cyclic and chronic neutropenia. Cancer Treat. Res. 157, 97-108 (2011).
135. Engelhard, D. et al. Cycling of peripheral blood and marrow lymphocytes in cyclic neutropenia. Proc. Natl Acad. Sci. USA 80, 5734-5738 (1983).
136. Leale, M. Reccurent furunculosis in an infant showing an unusual blood picture. JAMA 23, 1845-1855 (1910).
137. Reimann, H. A. Periodic disease; a probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. JAMA 136, 6 (1948).
138. Palmer, S. E., Stephens, K. & Dale, D. C. Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis. Am. J. Med. Genet. 66, 413-422 (1996).
139. Dingli, D., Antal, T., Traulsen, A. & Pacheco, J. M. Progenitor cell self-renewal and cyclic neutropenia. Cell Prolif. 42, 330-338 (2009).
140. Schmitz, S., Franke, H., Wichmann, H. E. & Diehl, V. The effect of continuous G?CSF application in human cyclic neutropenia: a model analysis. Br. J. Haematol. 90, 41-47 (1995).
141. Schmitz, S., Franke, H., Loeffler, M., Wichmann, H. E. & Diehl, V. Model analysis of the contrasting effects of GM?CSF and G?CSF treatment on peripheral blood neutrophils observed in three patients with childhood?onset cyclic neutropenia. Br. J. Haematol. 95, 616-625 (1996).
142. Østby, I. & Winther, R. Stability of a model of human granulopoiesis using continuous maturation. J. Math. Biol. 49, 501-536 (2004).
143. Lei, J. & Mackey, M. C. Multistability in an age-structured model of hematopoiesis: cyclical neutropenia. J. Theor. Biol. 270, 143-153 (2011).
144. Lei, J. & Mackey, M. C. Understanding and treating cytopenia through mathematical modeling. Adv. Exp. Med. Biol. 844, 279-302 (2014).
145. Dale, D. C. & Mackey, M. C. Understanding, treating and avoiding hematological disease: better medicine through mathematics? Bull. Math. Biol. 77, 739-757 (2015).
146. Schultz, W. Gangräneszierende prozesse und defekt des granulozytensystems [German]. Dtsch. Med. Wochenschr. 48, 1495-1496 (1922).
147. Friedemann, U. Agranulocytic angina. Med. Klin. 19, 1357 (1923).
148. Prendergast, D. A. Case of agranulocytic angina. Can. Med. Assoc. J. 17, 446-447 (1927).
149. Hitzig, W. H. Familial neutropenia with dominant hereditary factor and hypergammaglobulinemia [German]. Helv. Med. Acta 26, 779-784 (1959).
150. Person, R. E. et al. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat. Genet. 34, 308-312 (2003).
151. Hernandez, P. A. et al. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat. Genet. 34, 70-74 (2003).
152. Makaryan, V. et al. TCIRG1?associated congenital neutropenia. Hum. Mutat. 35, 824-827 (2014).
153. Dong, F. et al. Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. Proc. Natl Acad. Sci. USA 91, 4480-4484 (1994).
154. Ward, A. C., van Aesch, Y. M., Schelen, A. M. & Touw, I. P. Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia. Blood 93, 447-458 (1999).
155. Carlsson, G. et al. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J. Periodontol. 77, 744-751 (2006).