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

• Published in: Annals of hematology Vol. 98; no. 2; pp. 271 - 280
• Main Authors: Yabe, Miharu, Koike, Takashi, Ohtsubo, Keisuke, Imai, Eri, Morimoto, Tsuyoshi, Takakura, Hiromitsu, Koh, Katsuyoshi, Yoshida, Kenichi, Ogawa, Seishi, Ito, Etsuro, Okuno, Yusuke, Muramatsu, Hideki, Kojima, Seiji, Matsuo, Keitaro, Mori, Minako, Hira, Asuka, Takata, Minoru, Yabe, Hiromasa
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2019; Springer Nature B.V
• Subjects: Anemia; Bone marrow; Hematology; Medical prognosis; Medicine; Medicine & Public Health; Mutation; Oncology; Original Article; Stem cell transplantation; FA gene; Fanconi anemia; ALDH2; Cytogenetic abnormalities; Hematopoietic stem cell transplantation
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-018-3517-0

Fanconi anemia (FA) is a genetically and clinically heterogeneous disorder that predisposes patients to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). To study which genetic and phenotypic factors predict clinical outcomes for Japanese FA patients, we examined the FA genes, bone marrow karyotype, and aldehyde dehydrogenase-2 (
ALDH2
) genotype; variants of which are associated with accelerated progression of BMF in FA. In 88 patients, we found morphologic MDS/AML in 33 patients, including refractory cytopenia in 16, refractory anemia with excess blasts (RAEB) in 7, and AML in 10. The major mutated FA genes observed in this study were
FANCA
(
n
 = 52) and
FANCG
(
n
 = 23). The distribution of the
ALDH2
variant alleles did not differ significantly between patients with mutations in
FANCA
and
FANCG
. However, patients with
FANCG
mutations had inferior BMF-free survival and received hematopoietic stem cell transplantation (HSCT) at a younger age than those with
FANCA
mutations. In
FANCA
, patients with the c.2546delC mutation (
n
 = 24) related to poorer MDS/AML-free survival and a younger age at HSCT than those without this mutation. All patients with RAEB/AML had an abnormal karyotype and poorer prognosis after HSCT; specifically, the presence of a structurally complex karyotype with a monosomy (
n
 = 6) was associated with dismal prognosis. In conclusion, the best practice for a clinician may be to integrate the morphological, cytogenetic, and genetic data to optimize HSCT timing in Japanese FA patients.