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chronic myelogenous leukemia

Kamalika Sen, Arijita Sarkar, Ranjan Kumar Maji, Zhumur Ghosh, Sanjib Gupta, Tapash Chandra Ghosh
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation or abnormal accumulation of granulocytic cell line without the depletion of their capacity to differentiate. A reciprocal chromosomal translocation proceeding to the 'Philadelphia chromosome', involving the ABL proto-oncogene and BCR gene residing on Chromosome 9 and 22 respectively, is observed to be attributed to CML pathogenesis. Recent studies have been unraveling the crucial role of genomic 'dark matter' or the non-coding repertoire in cancer initiation and progression...
October 12, 2016: Molecular BioSystems
Nicolas Gaboriaud-Kolar, Vasillios Myrianthopoulos, Konstantina Vougogiannopoulou, Panagiotis Gerolymatos, David A Horne, Richard Jove, Emmanuel Mikros, Sangkil Nam, Alexios-Leandros Skaltsounis
Drug resistance in chronic myelogenous leukemia (CML) requires the development of new CML chemotherapeutic drugs. Indirubin, a well-known mutikinase inhibitor, is the major active component of "Danggui Longhui Wan", a Chinese traditional medicine used for the treatment of CML symptoms. An in-house collection of indirubin derivatives was screened at 1 μM on wild-type and imatinib-resistant T315I mutant CML cells. Herein are reported that only 15 analogues of the natural 6-bromoindirubin displayed potent cytotoxicity in the submicromolar range...
October 11, 2016: Journal of Natural Products
Thayalan Dineshkumar, Vemuri Suresh, Ramadas Ramya, Krishnan Rajkumar
Granulocytic sarcoma (GS) is an extremely rare condition involving infiltration of myeloblasts or immature myeloid cells in an extramedullary site. It is also known as chloroma, myeloid sarcoma or extramedullary myeloid tumor. It usually occurs concomitantly with acute myelogenous leukemia or with the onset of blastic phase of chronic myelogenous leukemia. On rare occasions, it evolves even before the onset of leukemias, and when it precedes leukemias without any overt signs, it is referred to as the primary type...
September 2016: Journal of Oral and Maxillofacial Pathology: JOMFP
Urszula Śliwińska-Hill
Imatinib mesylate (Imt) is a tyrosine kinase inhibitor mainly used in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML). Human serum transferrin is the most abundant serum protein responsible for the transport of iron ions and many endogenous and exogenous ligands. In this study the mechanism of interactions between the imatinib mesylate and all states of transferrin (apo-Tf, Htf and holo-Tf) has been investigated by fluorescence, ultraviolet-visible (UV-vis), circular dichroism (CD) and zeta potential spectroscopic methods...
September 24, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Naoki Mori, Mari Ohwashi-Miyazaki, Michiko Okada, Kentaro Yoshinaga, Masayuki Shiseki, Junji Tanaka
No abstract text is available yet for this article.
October 7, 2016: Acta Haematologica
Fengfeng Wang, Fei Meng, Lili Wang
MicroRNAs (miRNAs) are post-transcriptional regulators that regulate gene expression by binding to the 3' untranslated region of target mRNAs. Mature miRNAs transcribed from the miR-17-92 cluster have an oncogenic activity, which are overexpressed in chronic-phase chronic myelogenous leukemia (CML) patients compared with normal individuals. Besides, the tyrosine kinase activity of BCR-ABL oncoprotein from the Philadelphia chromosome in CML can affect this miRNA cluster. Genes with similar mRNA expression profiles are likely to be regulated by the same regulators...
2016: Frontiers in Genetics
Le Wen Xu, Yinghua Zhang, Yan Liu, Yan Ding
The current study reports a case of a patient with a chronic myelocytic leukemic fundus lesion, initially diagnosed in the Department of Ophthalmology, Rizhao People's Hospital (Rizhao, China). A male, 23-years-of-age, presented with a dark shadow in the front of the right eye, accompanied with blurred vision for 3 days (visual acuity of right eye, 0.4; visual acuity of left eye, 0.6). In addition, the patient had experienced gingival bleeding for 2 years, and recurrent upper respiratory infections for 1 year...
October 2016: Experimental and Therapeutic Medicine
(no author information available yet)
No abstract text is available yet for this article.
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Brian B Hasinoff, Daywin Patel, Xing Wu
Five clinically approved BCR-ABL1-targeted tyrosine kinase inhibitors (bosutinib, dasatinib, imatinib, nilotinib, and ponatinib) used for treating chronic myelogenous leukemia have been studied in a neonatal rat myocyte model for their relative ability to induce myocyte damage. This was done in order to determine if kinase inhibitor-induced myocyte damage was a consequence of inhibiting ABL1 (on-target effects), or due to a lack of kinase selectivity (off-target effects) since previous studies have come up with conflicting conclusions about whether imatinib-induced cardiotoxicity results directly from inhibition of ABL1...
September 30, 2016: Cardiovascular Toxicology
Karen Y P S Avelino, Isaac A M Frias, Norma Lucena-Silva, Renan G Gomes, Celso P de Melo, Maria D L Oliveira, César A S Andrade
In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL)...
September 22, 2016: Colloids and Surfaces. B, Biointerfaces
Y L Zu, Y L Zhang, J Zhou, H F Zhao, R R Gui, Z Li, S K Gao, Y P Song
To retrospectively analyze the efficacy of interferon plus imatinib (IM) in patients with chronic-phase chronic myelogenous leukemia(CML-CP)and ABL kinase domain mutations. The mutation rates of ABL kinase region in patients with Sokal score low, medium and high risk CML-CP were statistically significant (6.25%, 9.42% and 47.06%, P<0.05). The response rates of interferon plus IM versus second-generation TKI in CML-CP with non-T315I ABL kinase domain mutations were comparable (61.11% vs 65.52%, P>0.05)...
October 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Dilini C Gunasekara, Mary M Zheng, Tara Mojtahed, James R Woods, Tamer E Fandy, Mark V Riofski, Carlotta A Glackin, Hazem E Hassan, Julia Kirshner, David A Colby
Recent studies suggest that leukemia stem cells (LSCs) play a critical role in the initiation, propagation, and relapse of leukemia. Herein we show that (-)-15-methylene-eburnamonine, a derivative of the alkaloid (-)-eburnamonine, is cytotoxic against acute and chronic lymphocytic leukemias (ALL and CLL) and acute myelogenous leukemia (AML). The agent also decreases primary LSC frequency in vitro. The cytotoxic effects appear to be mediated via the oxidative stress pathways. Furthermore, we show that the compound kills AML, ALL, and CLL stem cells...
September 28, 2016: ChemMedChem
Yosuke Demizu, Norihito Shibata, Takayuki Hattori, Nobumichi Ohoka, Hiromi Motoi, Takashi Misawa, Takuji Shoda, Mikihiko Naito, Masaaki Kurihara
The manipulation of protein stability with small molecules has great potential as a technique for aiding the development of clinical therapies, including treatments for cancer. In this study, BCR-ABL protein degradation inducers called SNIPER(ABL) (Specific and Non-genetic inhibitors of apoptosis protein [IAP]-dependent Protein Erasers) were developed. The designed molecules contained two biologically active scaffolds: one was an imatinib derivative that binds to BCL-ABL and the other was a methyl bestatin that binds to cellular IAP 1 (cIAP1)...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Ying Lu, Ling-Ling Liu, Shou-Sheng Liu, Zhi-Gang Fang, Yong Zou, Xu-Bin Deng, Zi-Jie Long, Quentin Liu, Dong-Jun Lin
BACKGROUND: Chronic myelogenous leukemia (CML) is a hematological stem cell disorder. Tyrosine kinase inhibitors (TKIs) are the standard treatments for CML, but a number of patients fail to respond effectively due to gene mutations. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, has been shown to have anti-tumor effect on solid tumor whereas the anti-CML effect and its underlying mechanism have not been completely elucidated. METHODS: The cytotoxic effects of celecoxib and/or imatinib were evaluated by MTT assay...
2016: Journal of Translational Medicine
Yanli Jin, Jingfeng Zhou, Fang Xu, Bei Jin, Lijing Cui, Yun Wang, Xin Du, Juan Li, Peng Li, Ruibao Ren, Jingxuan Pan
Imatinib-insensitive leukemia stem cells (LSCs) are believed to be responsible for resistance to BCR-ABL tyrosine kinase inhibitors and relapse of chronic myelogenous leukemia (CML). Identifying therapeutic targets to eradicate CML LSCs may be a strategy to cure CML. In the present study, we discovered a positive feedback loop between BCR-ABL and protein arginine methyltransferase 5 (PRMT5) in CML cells. Overexpression of PRMT5 was observed in human CML LSCs. Silencing PRMT5 with shRNA or blocking PRMT5 methyltransferase activity with the small-molecule inhibitor PJ-68 reduced survival, serial replating capacity, and long-term culture-initiating cells (LTC-ICs) in LSCs from CML patients...
October 3, 2016: Journal of Clinical Investigation
Akihito Fujimi, Hiroki Sakamoto, Yuji Kanisawa, Shinya Minami, Yasuhiro Nagamachi, Naofumi Yamauchi, Soushi Ibata, Junji Kato
A 55-year-old man with several comorbidities including idiopathic interstitial pneumonia under long-term corticosteroid therapy, longstanding myocardial infarction, chronic heart failure, paroxysmal atrial fibrillation, gastro-esophageal reflux disease, constipation, and history of paralytic ileus, was diagnosed with chronic myelogenous leukemia (CML) in the chronic phase. He also tested positive for anti-topoisomerase I antibodies without clinical diagnosis of any connective tissue disease, including systemic sclerosis...
September 16, 2016: Clinical Journal of Gastroenterology
Keisuke Kawamoto, Hiroaki Miyoshi, Noriaki Yoshida, Jun Takizawa, Hirohito Sone, Koichi Ohshima
Myeloid sarcoma (MS) is an extramedullary tumor of immature myeloid cells. We analyzed 131 patients with MS, including: (1) de novo MS; (2) MS with concomitant acute myeloid leukemia (AML); (3) MS following myelodysplastic syndrome, myeloproliferative neoplasm, or chronic myelogenous leukemia; and (4) MS as a recurrence of AML. The most common development site was the lymph node. Testicular lesions were statistically more frequent in MS as a recurrence of AML than in other types of MS (P=0.0183). MS tended to lack myeloid markers (myeloperoxidase was present in 63...
September 14, 2016: American Journal of Surgical Pathology
Huafeng Xie, Cong Peng, Jialiang Huang, Bin E Li, Woojin Kim, Elenoe C Smith, Yuko Fujiwara, Jun Qi, Giulia Cheloni, Partha P Das, Minh Nguyen, Shaoguang Li, James E Bradner, Stuart H Orkin
Tyrosine kinase inhibitors (TKIs) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia initiating cells (LICs) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs, required for colony formation, and survival and cell cycle progression of CML cell lines. A critical role for Ezh2 is supported by genetic studies in a mouse CML model...
September 14, 2016: Cancer Discovery
Bin Zhang, Su Chu, Puneet Agarwal, Victoria L Campbell, Lisa Hopcroft, Heather G Jørgensen, Allen Lin, Karl Gaal, Tessa L Holyoake, Ravi Bhatia
Treatment of chronic myelogenous leukemia (CML) with BCR-ABL tyrosine kinase inhibitors (TKI) fails to eliminate leukemia stem cells (LSC). Patients remain at risk for relapse, and additional approaches to deplete CML LSC are needed to enhance the possibility of discontinuing TKI treatment. We have previously reported that expression of the pivotal pro-inflammatory cytokine interleukin-1 (IL-1) is increased in CML bone marrow (BM). We show here that CML LSC demonstrated increased expression of the IL-1 receptors, IL-1RAP and IL-1R1, and enhanced sensitivity to IL-1-induced NF-κB signaling compared to normal stem cells...
September 12, 2016: Blood
Shilpi Khetarpal, Apra Sood, Steven D Billings
Keratosis pilaris (KP) is a disorder of follicular keratinization that is characterized by keratin plugs in the hair follicles with surrounding erythema. A 46-year-old man with chronic myelogenous leukemia (CML) was started on nilotinib, a second generation tyrosine kinase inhibitor (TKI). Two months later the patient noticed red bumps on the skin and patchy hair loss on the arms, chest, shoulders, back, and legs. Cutaneous reactions to nilotinib are the most frequent non-hematologic adverse effects reported...
2016: Dermatology Online Journal
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