Associations of complementation group, ALDH2 genotype, and clonal abnormalities with hematological outcome in Japanese patients with Fanconi anemia

Yabe, Miharu; Kitahara, Takashi; Ohtsubo, Kohichiro; Imai, Eri; Morimoto, Takahiro; Takakura, Hiromitsu; Koh, Katsuyoshi; Yoshida, Kenichi; Ogawa, Seishi; Ito, Etsuro; Muramatsu, Hideki; Kojima, Seiji; Matsuo, Keitaro; Mori, Minako; Hira, Asuka; Takata, Minoru; Yabe, Hiromasa

doi:10.1007/s00277-018-3517-0

Cited by 19 publications

(20 citation statements)

References 30 publications

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“…The 21 patients displayed a wide range of clinical phenotype and genetic variation spectrum that all physiological systems were involved (Table 1), and the responsible mutations were detected in six different genes (Figure 1, Table 3). In keeping with other studies, bone marrow dysplasia and abnormal karyotypes were prevailing (65% and 42.11%, respectively ) and highly consistent [14,30], denoting the risk of hematologic malignant transformation, especially the ones with aberration in chromosome 7, which is the most prevalent cytogenetic abnormality in pediatric MDS and indicates an adverse long-term outcome even after HSCTs in MDS/AML patients [31]. ALDH2-G/A and ALDH-A/A genotypes are confirmed to be associated with more severe hematologic phenotype and more adverse outcomes of FA in Asian patients [13,14].…”

Section: Discussionsupporting

confidence: 92%

“…All patients in our cohort presented with a more severe hematologic manifestation and the proportion of patients who received HSCTs was higher than that of most studies [3][4][5][6]14,32]. Although BMF is the typical and most prevalent feature, our data may not reflect the actual behavior of FA since all the patients were referred to our institute seeking for HSCTs.…”

Section: Discussionmentioning

confidence: 67%

“…Inactivating ALDH2 variant (rs671 c.1510G>A/p.E504L) is highly prevalent in east Asia and can abolish ALDH2 activity by a dominantnegative effect [12]. ALDH2-A/A and ALDH2-G/A genotypes have been proved related to accelerated progression of BMF and malignant transformation in FA patients [13,14].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Nie

Zhang

Wang

et al. 2020

Preprint

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Background: Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet.Methods: We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA.Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied.Results: A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2 -G/A genotype have a significantly younger age of BMF onset ( p =0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection. Conclusion: The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Nie

Zhang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The 21 patients displayed a wide range of clinical phenotype and genetic variation spectrum that all physiological systems were involved (Table 1), and the responsible mutations were detected in six different genes (Figure 1, Table 3). In keeping with other studies, bone marrow dysplasia and abnormal karyotypes were prevailing (65% and 42.11%, respectively ) and highly consistent [14,30], denoting the risk of hematologic malignant transformation, especially the ones with aberration in chromosome 7, which is the most prevalent cytogenetic abnormality in pediatric MDS and indicates an adverse long-term outcome even after HSCTs in MDS/AML patients [31]. ALDH2-G/A and ALDH-A/A genotypes are con rmed to be associated with more severe hematologic phenotype and more adverse outcomes of FA in Asian patients [13,14].…”

Section: Discussionsupporting

confidence: 92%

“…All patients in our cohort presented with a more severe hematologic manifestation and the proportion of patients who received HSCTs was higher than that of most studies [3][4][5][6]14,32]. Although BMF is the typical and most prevalent feature, our data may not re ect the actual behavior of FA since all the patients were referred to our institute seeking for HSCTs.…”

Section: Discussionmentioning

confidence: 66%

Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Nie

Zhang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Fanconi anemia (FA) is the most common inherited bone marrow failure (BMF) syndrome with 22 related genes identified. The ALDH2 rs671variant has been proved related to accelerate the progression of BMF in FA patients. The phenotype and genetic basis of Chinese FA patients have not been investigated yet.Methods: We analyzed the 22 FA-related genes of 63 BMF patients suspected to be FA. Clinical manifestations, morphological and cytogenetic feathers, ALDH2 genotypes, treatment, and outcomes of the definite cases were retrospectively studied.Results: A total of 21 patients were confirmed the diagnosis of FA with the median age of BMF onset was 4-year-old. The number of patients manifested as congenital malformations and growth retardation were 20/21 and 14/21, respectively. BM dysplasia and cytogenetic abnormalities were found in 13/20 and 8/19 patients. All the patients with abnormal karyotypes also manifested as BM dysplasia or had evident blasts. Thirty-five different mutations were identified involving six genes and including twenty novel mutations. FANCA mutations contributed to 66.67% of cases. Eight patients harboring ALDH2-G/A genotype have a significantly younger age of BMF onset (p=0.025). Within the 19 patients adhering to continuous follow-up, 15 patients underwent hematopoietic stem cell transplantations (HSCTs). During the 29 months of follow-up, 8/19 patients died, seven of which were HSCT-related, and one patient who did not receive HSCT died from severe infection.Conclusions: The phenotypic and genetic spectrum of Chinese FA patients is broad. Bone marrow dysplasia and cytogenetic abnormalities are prevalent and highly consistent. The overall outcome of HSCTs is disappointing. Nationwide multicenter studies are needed for the rarity and adverse outcome of this disease.

show abstract

Long-term outcome in patients with Fanconi anemia who received hematopoietic stem cell transplantation: a retrospective nationwide analysis

et al. 2020

View full text Add to dashboard Cite

Associations of complementation group, ALDH2 genotype, and clonal abnormalities with hematological outcome in Japanese patients with Fanconi anemia

Cited by 19 publications

References 30 publications

Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies

Long-term outcome in patients with Fanconi anemia who received hematopoietic stem cell transplantation: a retrospective nationwide analysis

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