Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by 
congenital and developmental abnormalities, hypersensitivity to DNA 
cross-linking agents such as mitomycin C (MMC), and strong predisposition to 
acute myeloid leukemia (AML). In this article, we describe clinical and 
molecular findings in a boy with a severe FA phenotype who developed AML by the 
age of 2. Although he lacked a strong family history of cancer, he was 
subsequently shown to carry biallelic mutations in the FANCD1/BRCA2 gene. These 
included an IVS7 splice-site mutation, which is strongly associated with early 
AML in homozygous or compound heterozygous carrier status in FA-D1 patients. 
Myeloid leukemia cells from this patient have been maintained in culture for 
more than 1 year and have been designated as the SB1690CB cell line. Growth of 
SB1690CB is dependent on granulocyte macrophage colony stimulating factor or 
interleukin-3. This cell line has retained its MMC sensitivity and has undergone 
further spontaneous changes in the spectrum of cytogenetic aberrations compared 
with the primary leukemia. This is the second AML cell line derived from an 
FA-D1 patient and the first proof that malignant clones arising in FA patients 
can retain inherited MMC sensitivity. As FA-derived malignancies are normally 
not very responsive to treatment, this implies there are important mechanisms of 
acquiring correction of the cellular FA phenotype that would explain the poor 
chemoresponsiveness observed in FA-associated malignancies and might also play a 
role in the initiation and progression of cancer in the general population.