title: Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: first report.
abstract: We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91(phox) subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL.
authors.affiliation: Department of Pediatrics, Meir General Hospital, Kfar Saba, Israel. baruchw@clalit.org.il
authors.forename: Baruch
authors.initials: B
authors.lastname: Wolach
authors.forename: Shifra
authors.initials: S
authors.lastname: Ash
authors.forename: Ronit
authors.initials: R
authors.lastname: Gavrieli
authors.forename: Batia
authors.initials: B
authors.lastname: Stark
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D009679:Nuclear Family; D010375:Pedigree; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases