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Acute myeloid leukemia (AML) mesenchymal stem cells (MSCs) play an essential role in protecting leukemic cells from chemotherapeutic agents through activating a wide range of adhesion molecules and cytokines. Thus, more attention should be paid to attenuate the protection of leukemic cells by MSCs. By examining the gene expression files of MSCs from healthy donors and AML patients through high-throughput microarrays, we found that interleukin (IL)-6 was an important cytokine secreted by AML MSCs to protect leukemic cells, contributing to disease progression. Strikingly, Aurora A (AURKA) was activated by IL-6, offering a new target to interfere with leukemia. Importantly, a novel AURKA inhibitor, PW21, showed excellent AURKA kinase inhibitory activities and attenuated the interaction of leukemic cells and the microenvironment. PW21 inhibited MSC-induced cell proliferation, colony formation, and migration, and it induced cell apoptosis. Mechanically, PW21 could inhibit IL-6 secreted by MSCs. Moreover, we found that PW21 displayed a strong anti-leukemia effect on non-obese diabetic (NOD)-severe combined immunodeficiency (SCID) and murine MLL-AF9 leukemic models. PW21 significantly prolonged the survival of leukemic mice and eliminated the leukemic progenitor cells. AURKA inhibitor PW21 could provide a new approach for treatment of leukemia through blocking the protection by the leukemic microenvironment in clinical application.

A central tenet of theoretical cryptography is the study of the minimal assumptions required to implement a given cryptographic primitive. One such primitive is the one-time memory (OTM), introduced by Goldwasser, Kalai, and Rothblum [CRYPTO 2008], which is a classical functionality modeled after a non-interactive 1-out-of-2 oblivious transfer, and which is complete for one-time classical and quantum programs. It is known that secure OTMs do not exist in the standard model in both the classical and quantum settings. Here, we propose a scheme for using quantum information, together with the assumption of stateless ($i.e.$, reusable) hardware tokens, to build statistically secure OTMs. Via the semidefinite programming-based quantum games framework of Gutoski and Watrous [STOC 2007], we prove security for a malicious receiver making at most 0.114$n$ adaptive queries to the token (for $n$ the key size), in the quantum universal composability framework, but leave open the question of security against a polynomial amount of queries. Compared to alternative schemes derived from the literature on quantum money, our scheme is technologically simple since it is of the "prepare-and-measure" type. We also give two impossibility results showing certain assumptions in our scheme cannot be relaxed.

Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapyinduced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDF1/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

Abstract Background Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. Methods To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH). Results Results showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). However, CDKN2 deletion carriers demonstrated higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (P = 0.006), and upregulation of CD20 expression (P = 0.001). Moreover, deletions of CDKN2 resulted in lower rates of complete molecular response (undetectable BCR/ABL), increased cumulative incidence of relapse, short overall survival (OS), and disease-free survival (DFS) time (P