The Progress of Next Generation Sequencing in the Assessment of Myeloid Malignancies

The introduction and advances on next-generation sequencing have led to novel ways to integrate simultaneous assessment of multiple target genes in routine laboratory analysis. Assessment of myeloid neoplasms with targeted next-generation sequencing panels shows evidence to improve diagnosis, assist therapeutic decisions, provide better information about prognosis, and better detection of minimal residual disease. Herein, we provide information for application and utilization of next-generation sequencing studies with a focus on the most important mutations in acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, and other myelodysplastic/myeloproliferative neoplasms in order to integrate them into the daily clinical practice

Cutting Edge: IL-5 Primes Th2 Cytokine-Producing Capacity in Eosinophils through a STAT5-Dependent Mechanism

Abstract Both type-2 CD4+ Th cells (CD4+Th2) and type-2 innate effector cells play critical roles in generating type-2 immunity that can either be protective against parasitic infection or cause tissue damage in allergy and asthma. How innate effector cells acquire the capacity to produce Th2 cytokines is not entirely known. We previously showed that IL-4 induced differentiation of Th2 cytokine-producing eosinophils. To determine whether other Th2 cytokines can also induce Th2 cytokine-producing capacity in innate effector cells, we cultured bone marrow progenitor cells in the presence of various Th2 cytokines. IL-5, but not IL-13 or IL-25, primed bone marrow progenitor cells to differentiate into robust IL-4-producing cells. The majority of IL-4-producing cells induced by IL-5 were eosinophils. Importantly, IL-5 completely depended on STAT5 to promote IL-4-producing capacity in eosinophils. Thus, our study demonstrates that IL-5 functions as a potent factor that drives bone marrow progenitor cells into IL-4-producing eosinophils

Case Report A Case of Cutaneous Plasmablastic Lymphoma in HIV/AIDS with Disseminated Cryptococcus

We present a case of a patient with HIV/AIDS who presented with a tender left lower extremity cutaneous mass over a site of previous cryptococcal infection and was found to have plasmablastic lymphoma (PBL). The incidence of PBL is estimated to account for less than 5% of all cases of non-Hodgkin lymphoma (NHL) in HIV-positive individuals. In fact, there were only two reports of extraoral PBL at the time of a 2003 review. PBL in HIV-positive individuals is an aggressive malignancy that tends to occur in middle-aged males with low CD4 counts, high viral loads, and chronic HIV infection. The definitive diagnosis can be made with biopsy which typically shows malignant lymphoid cells that stain positive for plasma cell markers and negative for B-cell markers. The most common treatment is chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, but the overall survival rate is poor despite its relative responsiveness to chemotherapy. This case highlights the challenges that remain in improving clinical outcomes, the importance of antiretroviral therapy and HIV disease control, and a potential association between a chronic inflammatory state caused by disseminated Cryptococcus and tumorigenesis in individuals with PBL

MÜELLİFİ BİLİNMEYEN BİR ESER: “HİKÂYE-İ MUCİZÂTÜ’N-NEBİ”

Bu çalışmada Millî Kütüphane kayıtlarında Ankara Adnan Ötüken İl Halk Kütüphanesi Koleksiyonunda yer alan 06 Hk 4334/1 arşiv numaralı yazmanın 1b- 20a varakları arasında bulunan “Hikâye-i Mucizâtü’n-Nebi” isimli eser Arap harflerinden günümüz harflerine transkripsiyonlu olarak aktarılarak tanıtılmıştır. Yazmada eserin müellifi veya müstensihi, telif veya istinsah tarihi ile ilgili herhangi bir kayıt yoktur. Yazma içinde bir eser daha vardır. Bu eser yazmanın 20b- 31b varakları arasında yer alır. Bu eserde H 994 (M 1585/ 1586) tarihinde geçtiği ifade edilen bir olay çevresinde dinî bilgiler verilmektedir. Hikâye-i Mucizâtü’n-Nebi isimli yazma eserde eserin müellifi, müstensihi, telif veya istinsah tarihine ait bir kayıt bulunmasa da yazma içinde aynı kalemden çıkan ve 20b- 31b varakları arasında bulunan H 994 (M 1585/ 1586) tarihinde Sultan Murad devrinde geçen bir olay üzerine kurulan ve dini bilgiler içeren ikinci eserden hareketle Hikâye-i Mucizâtü’n-Nebi’nin H 994 tarihinde veya daha sonra kaleme alınmış olabileceğini düşünmek yerinde olacaktır

Aggressive NK-cell leukemia: A rare entity with diagnostic and therapeutic challenge

Aggressive natural killer cell leukemia (ANKL) is a rare neoplasm of mature natural killer cells, with an extremely poor overall survival, which is almost always EBV related, with majority of cases reported in East Asia. Here we report the case of an ANKL presenting in a young Hispanic male with secondary hemophagocytosis. Aggressive clinical course, high EBV DNA levels and leukemic presentation, often with associated hemophagocytosis, should raise suspicion of an NK/T-cell neoplasm like ANKL. Due to significant diagnostic overlap with extranodal NK/T-cell lymphoma, nasal type (ENKL), accurate diagnostic classification is crucial due to differing treatment and prognosis. L-asparaginase including chemotherapy followed by allogeneic stem cell transplantation appears to slightly prolong overall survival, but relapse is almost inevitable. Clinical monitoring of EBV DNA levels shows good correlation with disease activity

SUMOylation Confers Posttranslational Stability on NPM-ALK Oncogenic Protein

Nucleophosmin-anaplastic lymphoma kinase–expressing (NPM-ALK+) T-cell lymphoma is an aggressive form of cancer that commonly affects children and adolescents. The expression of NPM-ALK chimeric oncogene results from the chromosomal translocation t(2;5)(p23;q35) that causes the fusion of the ALK and NPM genes. This translocation generates the NPM-ALK protein tyrosine kinase that forms the constitutively activated NPM-ALK/NPM-ALK homodimers. In addition, NPM-ALK is structurally associated with wild-type NPM to form NPM/NPM-ALK heterodimers, which can translocate to the nucleus. The mechanisms that sustain the stability of NPM-ALK are not fully understood. SUMOylation is a posttranslational modification that is characterized by the reversible conjugation of small ubiquitin-like modifiers (SUMOs) with target proteins. SUMO competes with ubiquitin for substrate binding and therefore, SUMOylation is believed to protect target proteins from proteasomal degradation. Moreover, SUMOylation contributes to the subcellular distribution of target proteins. Herein, we found that the SUMOylation pathway is deregulated in NPM-ALK+ T-cell lymphoma cell lines and primary lymphoma tumors from patients. We also identified Lys24 and Lys32 within the NPM domain as the sites where NPM-ALK conjugates with SUMO-1 and SUMO-3. Importantly, antagonizing SUMOylation by the SENP1 protease decreased the accumulation of NPM-ALK and suppressed lymphoma cell viability, proliferation, and anchorage-independent colony formation. One possible mechanism for the SENP1-mediated decrease in NPM-ALK levels was the increase in NPM-ALK association with ubiquitin, which facilitates its degradation. Our findings propose a model in which aberrancies in SUMOylation contribute to the pathogenesis of NPM-ALK+ T-cell lymphoma. Unraveling such pathogenic mechanisms may lead to devising novel strategies to eliminate this aggressive neoplasm