While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Shōbōgenzō: Yui Butsu yo Butsu [and] ShōjiJoan StambaughShōbōgenzō: Yui Butsu yo Butsu [and] Shōji = [parallel French title:] Shōbōgenzō :Seul Bouddha connaît Bouddha [and] Vie-mort: Extrait de Shōbōgenzō de Dōgen Zenji[,] Maître Zen de XIIièème Sieècle = [parallel English title:] Shōbōgenzō: Only Buddha Knows Buddha [and] Life-death: Extract from Shōbōgenzō by Dōgen Zenji[,] XIIth Century Zen Master. By Dōgen. Traduit du japonais et annoté par Eido Shimano (...) Rō shi et Charles Vacher = Translated from Japanese and annotated by Eido Shimano Rō shi and Charles Vacher [trilingual edition]. La Versanne, France: Encre Marine, 1999. Pp. 152.Eidō Shimano Rōshi and Charles Vacher have completed their second effort at translating selections from Dōgen's Shōbōgenzō into English and French. Their first effort was a translation of Uji (Being-time), an early work. Now later works follow: Yui Butsu yo Butsu (Only Buddha knows Buddha) and Shōji (Life-death).The most striking feature of the translation here of the "Yui Butsu yo Butsu" fascicle is a more meaningful rendering of the title. Whereas most other translations read "Only Buddha and Buddha"—which is at best enigmatic, if not [End Page 320] unintelligible—this translation has "Only Buddha knows Buddha," a distinct improvement. The fascicle deals with the ability to know and recognize other beings of the same kind: fish knowing the fishes' heart, birds finding the birds' trail. Four-legged animals have no inkling of the birds' trail; it lies outside their ken. Similarly, an ordinary person, lacking the Buddha-eye, cannot recognize a buddha, able to see only the outside surface, only attributes and not the traces or trails. "Trace" or "trail" is intended here in the sense not of anything left over or behind—a kind of defilement—but rather of an indicator of where a buddha has gone.The phrase immediately following "Only Buddha knows Buddha" and repeated throughout the fascicle much like a Leitmotif reads: naino gūjin, complete combustion. These words are not to be found in the Sanskrit "original" text of the Lotus Sūtra, but were formulated by Kumārajīva, the translator of the Lotus Sūtra into Chinese. He was thus inspired to capture the gist of the Suō tra: only Buddha knows Buddha: complete combustion. With these words the nonduality of the working and presencing of Buddha with that of the entire universe is given expression.It is the particular merit of this translation to formulate "Only Buddha knows Buddha," in contrast to other translations that have a nearly meaningless "Only Buddha and Buddha," and to recapture Kumārajīva's brilliant interpretive words "complete combustion." The two are inseparable. When only Buddha knows Buddha, complete combustion, that is, penetration and presencing, takes place, the nonduality of samsāra and nirvāna.To say that searching for the true self is the unavoidable fate of human beings (p. 79) sounds a bit deterministic. It would perhaps be preferable to say that it is the wish or desire of all human beings.Shōji (life-death) has been used in China and Japan to translate samsāra, the repeated cycles of birth and death. The brief fascicle "Shōji" emphasizes the non-duality of samsāra and Buddha (nirvāna). Buddha or awakening is to be found in samsāra, nowhere else. The commonsense attitude is that life turns into—becomes—death. In contrast, Doōgen states that life is a temporary condition with its before and after. Thus, life is beginningless. Death is a temporary condition with its before and after. Thus, death is deathless. If we crave life and abhor death, we lose the very life of the Buddha that is to be found nowhere else than in the midst of the whole of birth-life-death.The fascicle concludes with the admonition to remain unattached, yet to have compassion for all beings.This process of birth-life-death is not something that begins at physical birth and terminates with physical death, but is ongoing from moment to moment. Thus... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Reconfiguring Modernity: Concepts of Nature in Japanese Political IdeologyWilliam R. LaFleurReconfiguring Modernity: Concepts of Nature in Japanese Political Ideology. By Julia Adeney Thomas. Berkeley, Los Angeles, and London: University of California Press, 2001. Pp. xvi + 225.Books written by persons who self-identify as intellectual historians usually lend themselves more easily to review in history journals than in those that focus on philosophy. Reconfiguring Modernity: Concepts of Nature in (...) Japanese Political Ideology, Julia Adeney Thomas' study of certain Meiji period thinkers is such a book. In 2002 it was awarded the John K. Fairbank Prize in history. Taking a cue to step into her topic from an early essay by Robert Bellah, one in which he had written that "the concern for nature has been a pervasive one in much of modern Japanese thought,"1 Thomas specifies her own search: "It is now time to recover the historical mutability of that concept, and to describe precisely its politics at particular moments in Japan's confrontation with modernity, both within the dominant ideology of the moment and with the alternatives to it" (pp. 30-31).Thomas is among those American students of Japan apparently trained to challenge the massive amounts of excavational scholarship and mile-high reputations of Japanese scholars of Japan. She picks arguments with some of the most highly respected Japanese minds of the twentieth century: the late Maruyama Masao, the late Ienaga Saburō, and Matsumoto Sannosuke.Although Thomas' criticisms tend to focus on those portions of the works of these prolific scholars that have been translated into English,2 some of her criticisms are certainly interesting and possibly valid. For instance, Maruyama, "who repeatedly excoriated Japan's reliance on the political authority of nature (shizen) " (p. 16), envisioned modernity, surely desirable, as involving a move "against Chu Hsi Confucianism"—that is, "an inevitable turning away from nature (shizen) to invention (sakui)" (p. 17). Nevertheless, Maruyama's hero, Ogyū Sorai (1666-1728), had understood "the narrative of modernity" but, tragically, stepped "back from invention at the critical moment, unable, it would seem, to embrace it as the culmination of the historical process" (p. 19).Thomas, rightly I think, indicates that most left and liberal thinkers in Europe and America in the early and mid-twentieth century were skeptical of an invocation of the "natural" in the making of political theory.3 However, she stakes a claim to being part of a different generation, one that rejects the old binary opposition between nature and culture—as well as the further assumption that Western political thinking had successfully disengaged itself from invoking the category of what is natural. Taking a cue from Stephen Toulmin's demonstration of how many of Europe's modernizers embraced and used, rather than rejected, concepts of nature,4 Thomas claims that, at least for us who now live "'on the far side of modernity,' nature can be seen [End Page 172] as multivalent rather than the antonym in a series of binary opposites." In practice this means that for us now, "nature can no longer appear synonymous with the anti-modern, the past, the oppressive, or the Orient" (p. 25).I ask that the reader highlight the sentences above. They constitute what in my view is the most important and by far the most interesting move made in Refiguring Modernity. I will return to them below. First, however, I will recapitulate the progression of the book's chapters. They move in the pattern of linear history. The first, discussed already and titled "The Trouble with Nature," introduces the problem. The second, "The Topographical Imagination of Tokugawa Politics," deals with thinkers of the Tokugawa (Edo) period (1600-1868). Theirs was an era during which, although Chinese claims to being both topographically and morally central had long been dutifully accepted in Japan, strong-thinking Japanese argued that China's frequent dynastic changes demonstrated that "centralness need not be possessed physically to be enacted morally" (p. 42). By outdoing contemporaneous Chinese in terms of being Confucian, Neo-Confucian, or whatever it was that had its origins in China, Japanese and in some sense Japan as a whole were imagined to be the "real China."5... (shrink)