Leukaemia-related gene expression in bone marrow cells from patients with the preleukaemic disorder Shwachman-Diamond syndrome.
Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure disorder with cytopenia and a high propensity for myelodysplastic syndrome (MDS) and leukaemia, particularly acute myeloid leukaemia. The mechanism of leukaemogenesis in SDS is unknown. In accordance to the multi-hit theory of carcinogenesis, it is likely that several molecular and cellular hits occur before MDS/leukaemia become apparent. This study used oligonucleotide microarray to identify gene expression patterns, which were shown to be associated with leukaemogenesis, in marrow mononuclear cells of nine SDS patients without overt transformation compared to healthy controls. Among 154 known leukaemia-related genes, several oncogenes were found to be upregulated, including LARG, TAL1 and MLL, and of several tumour suppressor genes were downregulated, including DLEU1, RUNX1, FANCD2 and DKC1. Real time polymerase chain reaction confirmed statistically higher expression of LARG and TAL1 in SDS marrows. We conclude that SDS marrow mononuclear cells exhibit abnormal gene expression patterns, which might result in continuous stimulation favouring evolution or progression of malignant clones. Additional molecular and cytogenetic events are probably necessary for the malignant process to be irreversible and complete.
Rujkijyanont
Piya
P
Marrow Failure and Myelodysplasia Program, Division of Haematology/Oncology, Department of Paediatrics, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
Beyene
Joseph
J
Wei
Kuiru
K
Khan
Fahad
F
Dror
Yigal
Y
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010198:Pancytopenia / Q000235:genetics*; D011289:Preleukemia / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome