Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
BACKGROUND
Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types.


METHODS
Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal hematopoietic cells (n = 8), normal non-hematopoietic tissues (n = 22) or human cancer tissues (n = 13).


RESULTS
This study revealed that e.g., the t(12;21) [ETV6-RUNX1] subtype of ALL and the t(15;17) [PML-RARA] subtype of AML had transcriptional programs similar to those in normal Pro-B cells and promyelocytes, respectively. Moreover, the 11q23/MLL subtype of ALL showed similarities with non-hematopoietic tissues. Strikingly however, most of the transcriptional programs in the other leukemic subtypes lacked significant similarity to approximately 100 gene sets derived from normal and malignant tissues.


CONCLUSIONS
This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia.
Andersson
Anna
A
Section of Clinical Genetics, Department of Laboratory Medicine, Lund University Hospital, Lund, Sweden. anna.andersson@med.lu.se
Edén
Patrik
P
Olofsson
Tor
T
Fioretos
Thoas
T
D015973:Gene Expression Regulation, Leukemic; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic; D015854:Up-Regulation; D000097764:ETS Translocation Variant 6 Protein
D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein