Differential expression of Ikaros isoforms in monozygotic twins with MLL-rearranged precursor-B acute lymphoblastic leukemia.
Infant leukemia associated with rearrangement of the MLL gene typically presents with high-risk clinical features. Relapse is common despite aggressive therapy and perturbations in signaling pathways may contribute to disease resistance. We evaluated twin 4-month-old monozygotic baby boys who presented with MLL-rearranged precursor-B acute lymphoblastic leukemia. Two different MLL/AF4 variants were found in both the twins, the first involving MLL intron 8 and AF4 intron 3 and the second stemming from translocations of MLL exon 10 and AF4 exon 4. We detected expression of the DNA-binding Ikaros isoforms, Ik1, Ikx+, Ik2 and the dominant-negative Ik4 Ikaros isoform in both patients. However, the dominant-negative Ik8 isoform was detected in only 1 boy, suggesting a common genetic ontogeny that was modulated by leukemic evolution. Further exploration of Ikaros expression in the background of MLL rearrangements may provide new insights into disease pathogenesis and could offer targets for novel chemotherapeutic agents.
Russell
Thomas
T
Department of Pediatrics, University of New Mexico Health Sciences Center and Cancer Research and Treatment Center, Albuquerque, NM, USA.
Oliver
Janet M
JM
Wilson
Bridget S
BS
Tarleton
Christy A
CA
Winter
Stuart S
SS
Meng
Xiangbing
X
D017766:Acid Anhydride Hydrolases / Q000235:genetics; D000208:Acute Disease; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D014178:Translocation, Genetic; D014430:Twins, Monozygotic; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D011495:Histone-Lysine N-Methyltransferase; D051740:Ikaros Transcription Factor; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D051941:fms-Like Tyrosine Kinase 3; D000099170:Bis(5'-adenosyl)triphosphatase; C497239:IKZF1 protein, human; C497422:KMT2A protein, human; C113855:MLL-AF4 fusion protein, human; C497970:FLT3 protein, human