Two novel high-risk adult B-cell acute lymphoblastic leukemia subtypes with high expression of CDX2 and IDH1/2 mutations.

The genetic basis of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unclear, and its clinical outcome remains unsatisfactory. This study aimed to advance the understanding of biological characteristics, improve disease stratification, and identify molecular targets of adult B-ALL. Adolescents and young adults (AYA) (15 to 39 years old, n = 193) and adults (40 to 64 years old, n = 161) with Philadelphia chromosome-negative (Ph-) B-ALL were included in this study.

Staurosporine and venetoclax induce the caspase-dependent proteolysis of MEF2D-fusion proteins and apoptosis in MEF2D-fusion (+) ALL cells.

MEF2D-fusion (M-fusion) genes are newly discovered recurrent gene abnormalities that are detected in approximately 5 % of acute lymphoblastic leukemia (ALL) cases. Their introduction to cells has been reported to transform cell lines or increase the colony formation of bone marrow cells, suggesting their survival-supporting ability, which prompted us to examine M-fusion-targeting drugs. To identify compounds that reduce the protein expression level of MEF2D, we developed a high-throughput screening system using 293T cells stably expressing a fusion protein of MEF2D and luciferase, in which the protein expression level of MEF2D was easily measured by a luciferase assay.

ZNF384-fusion proteins have high affinity for the transcriptional coactivator EP300 and aberrant transcriptional activities.

Zinc-finger protein 384 (ZNF384) fusion (Z-fusion) genes have recently been identified as recurrent fusion genes in B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) and have been detected in 7-17% of Philadelphia chromosome-negative BCP-ALL cases. We selected SALL4 and ID2 as potential Z-fusion-specific transcriptional targets that might lead to the differentiation disorder of Z-fusion-positive ALL. The introduction of EP300-ZNF384 and SYNRG-ZNF384 induced the expression of these genes.

Chromosomal translocation-mediated evasion from miRNA induces strong MEF2D fusion protein expression, causing inhibition of PAX5 transcriptional activity.

MEF2D fusion genes are newly discovered recurrent gene abnormalities that are detected in approximately 5% of acute lymphoblastic leukemia cases. We previously demonstrated that the vector-driven expression of MEF2D fusion proteins was markedly stronger than that of wild-type MEF2D; however, the underlying mechanisms and significance of this expression have yet to be clarified. We herein showed that the strong expression of MEF2D fusion proteins was caused by the loss of the target site of miRNA due to gene translocation.

Welder's pulmonary hemosiderosis associated with systemic iron overload following exacerbation of acute adult T-cell leukemia/lymphoma.

Herein, we describe a 61-year-old man diagnosed with pulmonary hemosiderosis following chemotherapy for acute adult T-cell leukemia/lymphoma (ATLL). Liver and heart biopsy confirmed hemosiderosis. ATLL progressed, and the patient died from multiorgan damage.

GM-CSF Autoantibody-positive Pulmonary Alveolar Proteinosis with Simultaneous Myeloproliferative Neoplasm.

Pulmonary alveolar proteinosis (PAP) is classified as autoimmune, secondary, or genetic. We herein describe a 69-year-old man with autoimmune PAP, simultaneously diagnosed with myeloproliferative neoplasm (MPN). Two years after the diagnosis, the MPN progressed to acute myeloid leukemia, and the patient died from an alveolar hemorrhage during remission induction chemotherapy.