| 1. |
- Zdebska, E, et al.
(författare)
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Glycoconjugate abnormalities in patients with congenital dyserythropoietic anaemia type I, II and III.
- 2001
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Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 114:4, s. 907-13
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Tidskriftsartikel (refereegranskat)abstract
- Congenital dyserythropoietic anaemia type II (CDA II) is well known for glycosylation abnormalities affecting erythrocyte membrane glycoconjugates that encompass hypoglycosylation of band 3 glycoprotein and accumulation of glycosphingolipids: lactotriaosylceramides, neolactotriaosylceramide and polyglycosylceramides. These abnormalities were not observed in erythrocytes from patients with CDA of either type I or III. Recently, however, we have described a CDA type I patient in Poland with identical, though less pronounced, glycoconjugate abnormalities to those observed in patients with CDA type II. The abnormalities included partial unglycosylation of O-linked glycosylation sites in glycophorin A. These abnormalities are now reported in three Bedouin patients from Israel with CDA type I. In addition, the erythrocyte membranes of these patients exhibited highly increased globotetraosylceramide content. Glycoconjugate abnormalities were also present in erythrocyte membranes from three patients from Northern Sweden with CDA type III but they almost exclusively affected glycosphingolipids. In erythrocytes of all patients examined including one with CDA type II, polyglycosylceramides were significantly hypoglycosylated although, on a molar basis, their contents in erythrocyte membranes were increased. Thus, glycoconjugate abnormalities of varying intensity occur in erythrocyte membranes from all patients with CDA that were investigated.
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| 4. |
- Hakkarainen, M, et al.
(författare)
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The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
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Tidskriftsartikel (refereegranskat)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
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| 5. |
- Hakkarainen, M, et al.
(författare)
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The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 141:23, s. 2853-2866
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Tidskriftsartikel (refereegranskat)abstract
- Biallelic germline ERCC6L2 variants strongly predispose to bone marrow failure (BMF) and myeloid malignancies characterized by somatic TP53-mutated clones and erythroid predominance. We present a series of 52 subjects (35 families) with ERCC6L2 biallelic germline variants collected retrospectively in 11 centers globally, including follow-up of 1165 person-years. At initial investigations, 32 individuals were diagnosed with BMF and 15 with a hematological malignancy (HM). Subjects presented with 19 different variants across ERCC6L2, and we identified a founder mutation c.1424delT in the Finnish patients. The median age of subjects at baseline was 18 years (range 2-65). Changes in complete blood count (CBC) were mild despite severe bone marrow hypoplasia and somatic TP53 mutations, with no significant difference between subjects with or without (HM). Signs of a progressive disease were increasing TP53 variant allele frequency, dysplasia in megakaryocytes and/or erythroid lineage, and erythroid predominance in bone marrow morphology. The median age at onset of HM was 37.0 years (95% CI: 31.5-42.5; range 12-65). Overall survival (OS) at 3 years was 95% (95% CI: 85-100) and 19% (95% CI: 0-39) for patients with BMF and HM, respectively. Patients with myelodysplastic syndrome or acute myeloid leukemia with mutated TP53 undergoing hematopoietic stem cell transplantation had a poor outcome: 3-year OS is 28% (95% CI: 0-61). Our results demonstrate the importance of early recognition and active surveillance of patients with biallelic germline ERCC6L2 variants.
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