Key Points The heat shock protein 90 inhibitor LAM-003 displays potent in vitro and in vivo activity as a single agent and combined with venetoclax. LAM-003 retains antileukemic activity against AML cells rendered resistant to FLT3 kinase inhibitors by mutation or stromal signaling.

No abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis. The risk of MDS is associated with aging and the accumulation of somatic mutations in hematopoietic stem cells and progenitors (HSPC). While advances in DNA sequencing in the past decade unveiled clonal selection driven by mutations in MDS, it is unclear at which stage the HSPCs are trapped or what prevents mature cells output. Single-cell-sequencing techniques in recent years have revolutionized our understanding of normal hematopoiesis by identifying the transitional cell states between classical hematopoietic hierarchy stages, and most importantly the biological activities behind cell differentiation and lineage commitment. Emerging studies have adapted these powerful tools to investigate normal hematopoiesis as well as the clonal heterogeneity in myeloid malignancies and provide a progressive description of disease pathogenesis. This review summarizes the potential of growing single-cell-sequencing techniques, the evolving efforts to elucidate hematopoiesis in physiological conditions and MDS at single-cell resolution, and discuss how they may fill the gaps in our current understanding of MDS biology.

In implant associated lymphomas, prothesis explantation and complete excision of any residual mass are the recommended approaches. Systemic chemotherapy is generally recommended for patients with locally advanced and disseminated diseases, mainly using treatment protocols routinely adopted for systemic ALCLs (e.g., CHOP, CHOEP, etc.). Limited data are available regarding the treatment of non-mammary implant associated ALCL. The first documented joint prosthesis associated ALCL patient was lost to follow-up while no adjuvant chemotherapy was considered in gluteal implant associated ALCL, however the patient was disease free. Our patient has received chemotherapy (CHOP regime) and was doing well at last follow-up.In conclusion, oncologists and pathologists should be more observant in patients who undergo silicone or non-silicone device implantation as these surgical procedures will continue to rise in various non-neoplastic and neoplastic lesions. Though the morphology and immunophenotyping of mammary and non-mammary implant associated ALCL is similar to ALK-negative ALCL, such cases need to be further investigated for DUSP22 or TP63 rearrangements as the latter carries dismal prognosis. The exact biological relationship between the implant device and ALCL needs to be addressed and explored at the molecular level.