Chromosomal aberrations associated with clonal evolution and leukemic transformation in fanconi anemia: clinical and biological implications

Abstract

Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, bone marrow failure, and extreme risk of leukemic transformation. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. Here, we review bone marrow findings in FA and discuss the clinical and biological implications of chromosomal aberrations associated with leukemic transformation.

Figure 1

FA-associated 3q aberrations. (a) conventional cytogenetics: outcuts of chromosome 2, 3, and 6 showing additional material at 2q, normal chromosomes 3, and an apparent deletion of 6q. (b) the conventional CGH shows a slight deviation at 2q, a gain of 3q25 to 3qter (enh), and a loss of material from 6q23 to 6qter (dim). (c) the FISH with whole chromosome paints wcp3 und wcp6 demonstrates two cell lines: one with material of chromosome 6 translocated to 2q and with material of 3 translocated to 6q; another cell line which carries only the translocation of material of chromosome 3 to 6q. Thus, the apparent deletion detected by conventional cytogenetics proved to be not a sole deletion of 6q but in addition a unbalanced translocation of 3q onto 6q. In addition, the patient had a monosomy 7 (data not shown). The karyotype according to ISCN 2009 in bone marrow cells was 45,XY,-7[2]/45,der(6)(6pter→6q22::3q25→3qter),-7[27]/45,der(2)(2pter→2q37::6q22→6qter),der(6)(6pter→6q22::3q25→3qter),-7[8].