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International Journal of Hematology

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https://www.readbyqxmd.com/read/28447249/guest-editorial-understanding-of-mpn-and-mds-mpn-based-on-molecular-pathogenesis-and-clinical-aspects
#1
EDITORIAL
Hironori Harada
No abstract text is available yet for this article.
April 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28447248/somatic-setbp1-mutations-in-myeloid-neoplasms
#2
REVIEW
Hideki Makishima
SETBP1 is a SET-binding protein regulating self-renewal potential through HOXA-protein activation. Somatic SETBP1 mutations were identified by whole exome sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute myeloid leukemia (sAML). Surprisingly, its recurrent somatic activated mutations are located at the identical positions of germline mutations reported in congenital Schinzel-Giedion syndrome...
April 26, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28444644/ponatinib-in-japanese-patients-with-philadelphia-chromosome-positive-leukemia-a-phase-1-2-study
#3
Arinobu Tojo, Taiichi Kyo, Kazuhito Yamamoto, Hirohisa Nakamae, Naoto Takahashi, Yukio Kobayashi, Tetsuzo Tauchi, Shinichiro Okamoto, Koichi Miyamura, Kiyohiko Hatake, Hiromi Iwasaki, Itaru Matsumura, Noriko Usui, Tomoki Naoe, Meera Tugnait, Narayana I Narasimhan, Stephanie Lustgarten, Heinrich Farin, Frank Haluska, Kazuma Ohyashiki
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2)...
April 25, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28439775/the-prognostic-significance-of-13q-deletions-of-different-sizes-in-patients-with-b-cell-chronic-lymphoproliferative-disorders-a-retrospective-study
#4
Shuhua Yi, Heng Li, Zengjun Li, Wenjie Xiong, Huimin Liu, Wei Liu, Rui Lv, Zhen Yu, Dehui Zou, Yan Xu, Gang An, Lugui Qiu
Patients with chronic lymphocytic leukemia (CLL) with 13q deletion as the sole cytogenetic abnormality usually have a favorable outcome, but the frequency of the 13q14 deletion and its impact on the outcome of other B-cell chronic lymphoproliferative disorders (BCLPDs) remain unclear. To further characterize this aberration, we investigated the prognostic significance of 13q deletion in 541 patients with BCLPDs. We performed fluorescence in situ hybridization (FISH) studies with 13q locus-specific LSI-D13S25 and LSI-RB1 probes...
April 24, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28429312/sox11-regulates-the-pro-apoptosis-signal-pathway-and-predicts-a-favorable-prognosis-of-mantle-cell-lymphoma
#5
Wenjuan Yang, Yanying Wang, Zhen Yu, Zengjun Li, Gang An, Wei Liu, Rui Lv, Liping Ma, Shuhua Yi, Lugui Qiu
Sex-determining region Y-box 11 (SOX11) is an important diagnostic marker in mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms and downstream effector pathways implicated in SOX11-driven transformation remain poorly understood. In the present study, we analyzed SOX11 expression in B-NHL, and used lentivirus-mediated RNA interference targeting SOX11 to investigate the resulting changes in cellular processes and the underlying mechanisms in MCL cell lines. We found that patients with higher SOX11 expression have superior overall survival (OS) and progression-free survival (PFS) compared to those with lower SOX11 expression...
April 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28425081/perisinusoidal-bone-marrow-involvement-by-lymphoma
#6
LETTER
Stefano Licci, Marco Rosati
No abstract text is available yet for this article.
April 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28421390/ofatumumab-combined-with-chlorambucil-for-previously-untreated-chronic-lymphocytic-leukemia-a-phase-i-ii-open-label-study-in-japan
#7
Kiyohiko Hatake, Michinori Ogura, Kohichi Takada, Masafumi Taniwaki, Fanghong Zhang, Taizo Fujita, Kiyoshi Ando
Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs...
April 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28409330/microrna-192-regulates-cell-proliferation-and-cell-cycle-transition-in-acute-myeloid-leukemia-via-interaction-with-ccnt2
#8
Shun Ke, Rui-Chao Li, Jun Lu, Fan-Kai Meng, Yi-Kuan Feng, Ming-Hao Fang
MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 18-22 nucleotides in length, which play an important role in malignant transformation. The roles of miR-192 as an oncogene or tumor suppressor in solid tumors have been previously reported. However, little is known about the role of miR-192 in human acute myeloid leukemia. The results of the present study indicate that miR-192 is significantly downregulated in specimens from acute myeloid leukemia patients. Functional assays demonstrated that overexpression of miR-192 in NB4 and HL-60 cells significantly inhibited cell proliferation compared with that in control cells, and induced G0/G1 cell cycle arrest, cell differentiation, and apoptosis in vitro...
April 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28409329/purification-of-leukemic-blast-cells-from-blood-smears-using-laser-microdissection
#9
Hidemasa Matsuo, Shuichi Shiga, Tsuyoshi Imai, Yasuhiko Kamikubo, Tsutomu Toki, Kiminori Terui, Etsuro Ito, Souichi Adachi
In treatment of acute myeloid leukemia (AML), prognostic factors, including gene mutation and abnormal gene expression, enable risk stratification of patients. However, in the case of a small proportion of leukemic blast cells, such as AML associated with Down syndrome (AML-DS), it is not possible to examine prognostic factors precisely due to the large proportion of normal cells. Here, we present a novel method for examining prognostic factors by making a smear on a membrane slide glass from a small amount of diagnostic specimen and collecting highly pure leukemic blast cells by laser microdissection (LMD)...
April 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28409328/long-term-treatment-with-bosutinib-in-a-phase-1-2-study-in-japanese-chronic-myeloid-leukemia-patients-resistant-intolerant-to-prior-tyrosine-kinase-inhibitor-treatment
#10
Naoto Takahashi, Chiaki Nakaseko, Yukio Kobayashi, Koichi Miyamura, Chiho Ono, Yuichiro Koide, Yosuke Fujii, Kazunori Ohnishi
This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3‒372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively...
April 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28405919/iron-overload-may-promote-alteration-of-nk-cells-and-hematopoietic-stem-progenitor-cells-by-jnk-and-p38-pathway-in-myelodysplastic-syndromes
#11
Yanni Hua, Chaomeng Wang, Huijuan Jiang, Yihao Wang, Chunyan Liu, Lijuan Li, Hui Liu, Zonghong Shao, Rong Fu
The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs...
April 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28405918/hepcidin-suppression-in-%C3%AE-thalassemia-is-associated-with-the-down-regulation-of-atonal-homolog-8
#12
Supranee Upanan, Andrew T McKie, Gladys O Latunde-Dada, Sittiruk Roytrakul, Chairat Uthaipibull, Peraphan Pothacharoen, Prachya Kongtawelert, Suthat Fucharoen, Somdet Srichairatanakool
Atonal homolog 8 (ATOH8) is defined as a positive regulator of hepcidin transcription, which links erythropoietic activity with iron-sensing molecules. In the present study, we investigated the association between hepcidin and ATOH8 expression in β-thalassemia. We found that inhibition of hepcidin expression in β-thalassemia is correlated with reduced ATOH8 expression. Hepatic hepcidin 1 (Hamp1) and Atoh8 mRNA expression were down-regulated in β-thalassemic mice. Hepcidin (HAMP) and ATOH8 mRNA expression were consistently suppressed in Huh7 cells cultured in medium supplemented with β-thalassemia patient serum...
April 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28401497/bortezomib-combined-with-standard-induction-chemotherapy-in-japanese-children-with-refractory-acute-lymphoblastic-leukemia
#13
Akihiro Iguchi, Yuko Cho, Minako Sugiyama, Yukayo Terashita, Tadashi Ariga, Yosuke Hosoya, Shinsuke Hirabayashi, Atsushi Manabe, Keisuke Hara, Tetsuya Aiba, Tsugumi Shiokawa, Hiroko Tada, Norihiro Sato
Bortezomib has been shown to be effective and well-tolerated in patients with refractory acute lymphoblastic leukemia (ALL) in the Therapeutic Advances in Childhood Leukemia trial. However, the safety and efficacy of bortezomib have not been evaluated in Japanese pediatric patients. Here, we report the results of a clinical trial designed to evaluate the safety of bortezomib combined with induction chemotherapy in Japanese children with refractory ALL. A total of six patients with B-precursor ALL were enrolled in this study...
April 11, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28390037/clinical-usefulness-of-the-dilute-russell-viper-venom-time-test-for-patients-taking-warfarin
#14
Kazunori Kanouchi, Hiroto Narimatsu, Okio Ohnuma, Keita Morikane, Akira Fukao
Warfarin use often causes false-positive results in the dilute Russell viper venom time test (DRVVT). Thus, three sets of guidelines-those presented by the International Society on Haemostasis and Thrombosis (ISTH), the British Committee for Standards in Haematology (BCSH), and the Clinical and Laboratory Standards Institute (CLSI)-are advocated. We evaluated the clinical usefulness of the testing methods recommended in these three guidelines using laboratory samples. Of the 242 samples from patients using warfarin, 38 were positive for lupus anticoagulant (LA)...
April 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28390036/marked-hypereosinophilia-and-rash-as-initial-presentation-of-acute-myeloid-leukemia-with-t-8-21
#15
LETTER
Shin Yeu Ong, Liam Pock Ho, Pei Ming Yeo, Heng Joo Ng, Ai Leen Ang
No abstract text is available yet for this article.
April 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28390035/primary-fungal-prophylaxis-in-acute-leukemia-patients-with-different-risk-factors-retrospective-analysis-from-the-caesar-study
#16
Rongli Zhang, Jing Chen, He Huang, Jun Ma, Fanyi Meng, Yongmin Tang, Jianda Hu, Xi Zhang, Yu Ji, Huisheng Ai, Yingmin Liang, Depei Wu, Xiaojun Huang, Mingzhe Han
Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factors is unclear. We analyzed 2015 Chinese AL patients who received a total of 2274 chemotherapy courses, including 1410 courses in acute myeloid leukemia (AML) patients and 864 courses in acute lymphocytic leukemia (ALL) patients. The IFD incidence was significantly higher among AML than ALL patients (11.8 vs. 7.1%, P < 0...
April 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28390034/diffuse-large-b-cell-lymphoma-with-a-bulky-mass-in-the-cranial-vault
#17
LETTER
Minoru Kanaya, Tomoyuki Endo, Daigo Hashimoto, Shogo Endo, Ryo Takemura, Kohei Okada, Kanako C Hatanaka, Yoshihiro Matsuno, Takanori Teshima
No abstract text is available yet for this article.
April 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28378056/analysis-of-adverse-events-associated-with-dasatinib-and-nilotinib-treatments-in-chronic-phase-chronic-myeloid-leukemia-patients-outside-clinical-trials
#18
Koung Jin Suh, Ji Yun Lee, Dong-Yeop Shin, Youngil Koh, Soo-Mee Bang, Sung-Soo Yoon, Seonyang Park, Inho Kim, Jeong-Ok Lee
We analyzed adverse events (AEs) in 201 chronic phase CML patients treated with nilotinib (n = 120) or dasatinib (n = 81) as first- or second-line therapy. The dasatinib group had significantly higher grade 3-4 AEs compared to the nilotinib group (22 vs. 54%, p < 0.001), and had more frequent dose reduction, interruption, and discontinuation (p < 0.001, p = 0.004, and p = 0.006, respectively). Of 59 patients who discontinued treatment, 47 (80%) discontinued treatment due to AEs; 50% of the AEs causing drug discontinuation were of grade 2 severity...
April 4, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28378055/ep300-znf384-fusion-gene-product-up-regulates-gata3-gene-expression-and-induces-hematopoietic-stem-cell-gene-expression-signature-in-b-cell-precursor-acute-lymphoblastic-leukemia-cells
#19
Akinori Yaguchi, Takeshi Ishibashi, Kazuki Terada, Hitomi Ueno-Yokohata, Yuya Saito, Junya Fujimura, Toshiaki Shimizu, Kentaro Ohki, Atsushi Manabe, Nobutaka Kiyokawa
ZNF384-related fusion genes are associated with a distinct subgroup of B-cell precursor acute lymphoblastic leukemias in childhood, with a frequency of approximately 3-4%. We previously identified a novel EP300-ZNF384 fusion gene. Patients with the ZNF384-related fusion gene exhibit a hematopoietic stem cell (HSC) gene expression signature and characteristic immunophenotype with negative or low expression of CD10 and aberrant expression of myeloid antigens, such as CD33 and CD13. However, the molecular basis of this pathogenesis remains completely unknown...
April 4, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28374143/dna-damage-response-and-hematological-malignancy
#20
REVIEW
Masatoshi Takagi
DNA damage is a serious threat to cellular homeostasis. Damaged DNA leads to genomic instability, mutation, senescence, and/or cell death. DNA damage triggers a cellular response called the DNA damage response (DDR), followed by activation of the DNA repair machinery. DDR both maintains cellular homeostasis and prevents cancer development. Germ line mutation of DDR-associated genes can lead to cancer-susceptible syndromes. Somatic mutation of DDR-associated genes has also been reported in various tumors, including hematological malignancies...
April 3, 2017: International Journal of Hematology
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