Uncommon Pediatric Tumors of the Thorax

Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia

“…et al, manuscript submitted). 1,2 Even applying a stringent definition, our data indicate that the preponderance of infant ALL is obatoclaxsensitive in vitro regardless of poor prognostic features, as evidenced by EC 50 s within clinically achievable concentrations. MLL-AF4 is the largest molecular cytogenetic subset within infant ALL.…”

“…16 Although EC 50 s were higher than in other subsets, 19 (68%) of 28 MLL-AF4 cases were obatoclax-sensitive, and even greater sensitivity was found in MLL-ENL cases, a historically refractory infant ALL subset with significantly worse survival. 1,16 In addition, most EC 50 s were well below that for normal PBMCs, suggesting that exposure requirements for target cell activity are lower than for normal blood cells.…”

“…et al, manuscript in preparation). [1][2][3] More-efficacious, better-tolerated therapies are urgent. MLL translocations, which occur in 75% of ALL in infants younger than 1 year, are associated with poor outcomes, but survival in MLL-germline (G) cases also is inferior compared with ALL in children younger than 1 year (Z.E.D.…”

Identification of CD34+ and CD34− leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia

“…[20][21][22] ALL in infants is biologically distinct from ALL in older children, with 70% to 80% of infant cases associated with MLL translocations. 23 Although long-term event-free survival rates of ;80% are reported in older children with ALL, prognosis for infants is at ;40%, and prognosis for infants diagnosed with MLL-rearranged leukemia is significantly poorer than in MLL-nonrearranged cases. [23][24][25] In some malignancies such as adult AML, malignant stem cells may play important roles both in the initiation of disease and in disease relapse.…”

“MOR” engineering of antibodies in ALL

“…1 A lthough the majority of children with ALL are cured, infants with B-cell precursor (BCP) ALL have an extremely poor outcome, with a 4-year event-free survival ,50%. 2 The MLL gene represents the most frequent cytogenetic abnormality in infants.…”