title: Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia.
abstract: We have analyzed the frequency and clinical significance of the MLL gene rearrangements in 42 cases of infant acute leukemias; including 37 cases of acute lymphoblastic leukemia (ALL) and five cases of acute myeloid leukemia (AML). MLL gene rearrangements were found in 27 of the 37 ALL cases (73 percent), and in all five AML cases. Cytogenetic studies showed 11q23 abnormalities in 24 of 27 ALL cases with MLL gene rearrangements. MLL gene rearrangements were significantly correlated with absence of CD10 expression and poor prognosis, but not with age under 6 months, hyperleukocytosis, myeloid-associated antigen expression, or CNS leukemia. The 3-year overall survival rate for ALL cases with MLL gene rearrangements was 5.3 +/- 5.2 percent, compared with 88.9 +/- 10.5 percent for cases with germline MLL (P=0.0001). Absence of CD10 expression was also associated with poor prognosis (9.9 +/- 6.6 percent vs 85.7 +/- 13.2 percent, P = 0.0003). Of the five AML cases, three have remained alive for 27 months to 67 months. These findings suggest that infant ALL with MLL gene rearrangement is strongly associated with poor prognosis. We consider that infant ALL should be treated on different chemotherapy protocols according to the presence or absence of MLL gene rearrangement.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Taki
authors.forename: K
authors.initials: K
authors.lastname: Ida
authors.forename: F
authors.initials: F
authors.lastname: Bessho
authors.forename: R
authors.initials: R
authors.lastname: Hanada
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: M
authors.initials: M
authors.lastname: Sako
authors.forename: M
authors.initials: M
authors.lastname: Tsuchida
authors.forename: M
authors.initials: M
authors.lastname: Seto
authors.forename: R
authors.initials: R
authors.lastname: Ueda
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D002894:Chromosomes, Human, Pair 4; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011519:Proto-Oncogenes; D012189:Retrospective Studies; D015996:Survival Rate; D014157:Transcription Factors; D014178:Translocation, Genetic; D016335:Zinc Fingers
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase