Heat conductance of the quantum Hall bulk.

The quantum Hall effect is a prototypical realization of a topological state of matter. It emerges from a subtle interplay between topology, interactions and disorder1-9. The disorder enables the formation of localized states in the bulk that stabilize the quantum Hall states with respect to the magnetic field and carrier density3. Still, the details of the localized states and their contribution to transport remain beyond the reach of most experimental techniques10-31. Here we describe an extensive study of the bulk's heat conductance. Using a novel 'multiterminal' short device (on a scale of 10 µm), we separate the longitudinal thermal conductance, [Formula: see text] (owing to the bulk's contribution), from the topological transverse value [Formula: see text] by eliminating the contribution of the edge modes24. When the magnetic field is tuned away from the conductance plateau centre, the localized states in the bulk conduct heat efficiently ([Formula: see text]), whereas the bulk remains electrically insulating. Fractional states in the first excited Landau level, such as the [Formula: see text] and [Formula: see text], conduct heat throughout the plateau with a finite [Formula: see text]. We propose a theoretical model that identifies the localized states as the cause of the finite heat conductance, agreeing qualitatively with our experimental findings.

ETV6-NCOA2 fusion induces T/myeloid mixed-phenotype leukemia through transformation of nonthymic hematopoietic progenitor cells.

Mixed-phenotype acute leukemia is a rare subtype of leukemia in which both myeloid and lymphoid markers are co-expressed on the same malignant cells. The pathogenesis is largely unknown, and the treatment is challenging. We previously reported the specific association of the recurrent t(8;12)(q13;p13) chromosomal translocation that creates the ETV6-NCOA2 fusion with T/myeloid leukemias. Here we report that ETV6-NCOA2 initiates T/myeloid leukemia in preclinical models; ectopic expression of ETV6-NCOA2 in mouse bone marrow hematopoietic progenitors induced T/myeloid lymphoma accompanied by spontaneous Notch1-activating mutations. Similarly, cotransduction of human cord blood CD34+ progenitors with ETV6-NCOA2 and a nontransforming NOTCH1 mutant induced T/myeloid leukemia in immunodeficient mice; the immunophenotype and gene expression pattern were similar to those of patient-derived ETV6-NCOA2 leukemias. Mechanistically, we show that ETV6-NCOA2 forms a transcriptional complex with ETV6 and the histone acetyltransferase p300, leading to derepression of ETV6 target genes. The expression of ETV6-NCOA2 in human and mouse nonthymic hematopoietic progenitor cells induces transcriptional dysregulation, which activates a lymphoid program while failing to repress the expression of myeloid genes such as CSF1 and MEF2C. The ETV6-NCOA2 induced arrest at an early immature T-cell developmental stage. The additional acquisition of activating NOTCH1 mutations transforms the early immature ETV6-NCOA2 cells into T/myeloid leukemias. Here, we describe the first preclinical model to depict the initiation of T/myeloid leukemia by a specific somatic genetic aberration.