A cross-linker-sensitive myeloid leukemia cell line from a 2-year-old boy with severe Fanconi anemia and biallelic FANCD1/BRCA2 mutations
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 molecul...
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Published in | Genes chromosomes & cancer Vol. 42; no. 4; pp. 404 - 415 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.04.2005
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Subjects | |
Online Access | Get full text |
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Summary: | 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. © 2005 Wiley‐Liss, Inc. |
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Bibliography: | ArticleID:GCC20153 Cancer Research UK istex:47CB6B99F8036266582EDBD5C97A3EB3477D2780 ark:/67375/WNG-2KK5RFW8-T Leukaemia Research Fund (UK) Clinical Research Fellowship Netherlands Organization for Health and Development Dutch Cancer Society ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Case Study-2 ObjectType-Feature-4 ObjectType-Report-1 ObjectType-Article-3 |
ISSN: | 1045-2257 1098-2264 |
DOI: | 10.1002/gcc.20153 |