1.Director of Cytogenetics Laboratory, Department of Pathology (Room 4023A), St. Jude Childrens Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA
The following information was obtained from 2 published reports of a multinational collaborative study of 497 pediatric patients with 11q23 abnormalities and ALL. In this study, some data for a few patients were unavailable.
Table 1. Frequency of five types of 11q23 abnormalities among three age groups of patients.
Table 2. The clinico-biological presenting features of 497 patients with ALL and 11q23/MLL rearrangement.
Leukemic cells from infants with ALL are significantly more resistant to prednisone and L-asparaginase in vitro than are leukemic cells from older patients with ALL. However, leukemic cells in infants are highly sensitive to cytosine arabinoside (ara-C). These findings were incorporated into two cooperative treatment protocols for infants with ALL: the international Interfant-99 protocol and a protocol of the Childrens Oncology Group in the United States.
New therapeutic regimens are needed to cure infants with 11q23 abnormalities and high-risk ALL. Recent studies have shown high levels of FLT3 expression in patients with MLL rearrangements; therefore, inhibitors of FLT3 (a tyrosine kinase) may prove to be beneficial.
Table 3. The impact of age and phenotype on the 5-year event-free survival (EFS) estimates for children with ALL and different types of 11q23 abnormality.
Molecular cytogenetic methods have shown that the frequency of MLL gene rearrangements exceeds that of 11q23 translocations detected by conventional cytogenetic methods. In ALL cases in which deletions and inversions affect the 11q23 band (both types of abnormality are associated with favorable clinical features and prognoses), FISH should be done to determine whether a cryptic rearrangement of MLL is present. In a few cases, an 11q23 translocation involves genes other than MLL. Because the translocation partners for 11q23 are markedly heterogeneous, additional molecular methods are needed to further assess the MLL gene in patients with an 11q23 abnormality. Information from such assessments can then be used to better stratify treatment groups.
Susana C Raimondi
11q23 rearrangements (KMT2A) in childhood acute lymphoblastic leukemia
Atlas Genet Cytogenet Oncol Haematol. 2004-02-01
Online version: http://atlasgeneticsoncology.org/haematological/1321/11q23childallid1321