Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

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IntroductionColloidal quantum dots (CQDs) offer advantages over conventional bulk inorganic semiconductors such as solution Low-temperature solution-processed high-effi ciency colloidal quantum dot (CQD) photovoltaic devices are developed by improving the interfacial properties of p-n heterojunctions. A unique conjugated polyelectrolyte, WPF-6-oxy-F, is used as an interface modifi cation layer for ZnO/PbS-CQD heterojunctions. With the insertion of this interlayer, the device performance is dramatically improved. The origins of this improvement are determined and it is found that the multifunctionality of the WPF-6-oxy-F interlayer offers the following essential benefi ts for the improved CQD/ZnO junctions: (i) the dipole induced by the ionic substituents enhances the quasi-Fermi level separation at the heterojunction through favorable energy band-bending, (ii) the ethylene oxide groups containing side chains can effectively passivate the interfacial defect sites of the heterojunction, and (iii) these effects occur without deterioration in the intrinsic depletion region or the series resistance of the device. All of the fi gures-of-merit of the devices are improved as a result of the enhanced built-in potential (electric fi eld) and the reduced interfacial charge recombination at the heterojunction. The benefi ts due to the WPF-6-oxy-F interlayer are generally applicable to various types of PbS/ZnO heterojunctions. Finally, CQD photovoltaic devices with a power conversion effi ciency of 9% are achievable, even by a solution process at room temperature in an air atmosphere. The work suggests a useful strategy to improve the interfacial properties of p-n heterojunctions by using polymeric interlayers.

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