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myeloproliferative

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https://www.readbyqxmd.com/read/28211153/the-prognostic-relevance-of-serum-lactate-dehydrogenase-and-mild-bone-marrow-reticulin-fibrosis-in-essential-thrombocythemia
#1
Mythri Mudireddy, Daniela Barraco, Curtis A Hanson, Animesh Pardanani, Naseema Gangat, Ayalew Tefferi
The 2016 World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (MPN) underscore the prognostically-relevant distinction between essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF). In addition, leukocytosis has been identified as an important prognostic marker in otherwise WHO-defined ET. However, controversy remains regarding the objectivity of morphologic criteria in distinguishing ET from pre-PMF and the precise prognostic cutoff values for leukocytosis...
February 17, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28205462/atypical-chronic-myeloid-leukemia-in-a-german-shepherd-dog
#2
Christina L Marino, Jimmy N S N Tran, Tracy Stokol
A 4-y-old neutered male German Shepherd Dog was presented with a 3-d duration of lethargy, restlessness, and vomiting. Physical examination revealed generalized lymphadenopathy, pale mucous membranes, systolic heart murmur, dehydration, and fever. Hematologic abnormalities included moderate-to-marked leukocytosis, characterized by neutrophilia with a left shift to progranulocytes and 2% presumptive myeloid blasts, marked anemia that was nonregenerative, and marked thrombocytopenia. Dysplasia was evident in neutrophils and platelets...
February 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28202867/gm-csf-autoantibody-positive-pulmonary-alveolar-proteinosis-with-simultaneous-myeloproliferative-neoplasm
#3
Naoto Imoto, Nakashima Harunori, Katsuya Furukawa, Naoyuki Tange, Atsushi Murase, Masaya Hayakawa, Masatoshi Ichihara, Yosuke Iwata, Hiroshi Kosugi
Pulmonary alveolar proteinosis (PAP) is classified as autoimmune, secondary, or genetic. We herein describe a 69-year-old man with autoimmune PAP, simultaneously diagnosed with myeloproliferative neoplasm (MPN). Two years after the diagnosis, the MPN progressed to acute myeloid leukemia, and the patient died from an alveolar hemorrhage during remission induction chemotherapy. Throughout the clinical course, no progression of PAP was observed, despite the progression to leukemia. There are few reports of autoimmune PAP with hematological malignancy, and this case demonstrated that an evaluation for GM-CSF autoantibodies is important for distinguishing the autoimmune and secondary forms of PAP, even if the patient has hematological malignancy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28190862/acute-myeloid-leukemia-with-t-3-21-q13-q22-a-novel-simple-variant-of-the-21q22-runx1-translocation
#4
Yuka Tsuruoka, Hirotaka Sakai, Akiko Uchida, Yu Uemura, Kazuyuki Sato, Satoshi Yokoi, Yuji Nishio, Manabu Matsunawa, Yoshinori Suzuki, Yasushi Isobe, Masayuki Kato, Naoto Tomita, Yasuyuki Inoue, Ikuo Miura
A 69-year-old man diagnosed with leukocytosis was referred to our hospital in July 201X. The patient was diagnosed as having a myelodysplastic/myeloproliferative neoplasm. However, he presented with leukemia 2 months later. Chromosomal analysis of a bone marrow sample documented that this patient had a normal karyotype. The patient was successfully treated with idarubicin and cytarabine, and he underwent three courses of consolidation therapy. However, he suffered a relapse in May of the following year. A cytogenetic analysis revealed the presence of a t (3;21) (q13;q22) translocation, and fluorescence in situ hybridization of metaphase spreads detected three signals corresponding to the runt related transcription factor 1 (RUNX1) on the derivative chromosomes 3 and 21, besides the normal chromosome 21...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28188970/refractory-anemia-with-ring-sideroblasts-rars-and-rars-with-thrombocytosis-rars-t-2017-update-on-diagnosis-risk-stratification-and-management
#5
Mrinal M Patnaik, Ayalew Tefferi
DISEASE OVERVIEW: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T). DIAGNOSIS: MDS-RS is a lower risk MDS, with single or multilineage dysplasia (SLD/MLD), <5% bone marrow (BM) blasts and ≥15% BM RS (≥5% in the presence of SF3B1 mutations)...
March 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28186604/-clinical-and-genetic-features-of-a-patient-with-myeloid-neoplasm-in-association-with-pdgfra-and-evi1-gene-rearrangements
#6
Wenmin Han, Hongying Chao, Min Zhou, Ling Cen, Suning Chen, Xuefeng He, Xuzhang Lu
OBJECTIVE: Todelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements. METHODS: Clinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient. RESULTS: The patient has featured recurrent rash, joint pain, and intermittent fever. Laboratory tests showed hyperleukocytosis and marked eosinophilia...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28185911/transcriptome-analysis-of-monozygotic-twin-brothers-with-childhood-primary-myelofibrosis
#7
Nan Ding, Zhaojun Zhang, Wenyu Yang, Lan Ren, Yingchi Zhang, Jingliao Zhang, Zhanqi Li, Peihong Zhang, Xiaofan Zhu, Xiaojuan Chen, Xiangdong Fang
Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder in human bone marrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However, these mutations are rarely detected in children, suggesting a difference in the pathogenesis of childhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twin pair with typical childhood PMF. The twin exhibited different clinical outcomes despite following the same treatment regimen. The transcriptomic profiles of patient samples after drug treatment (E2 and Y2) were significantly different between the twin pair, which is consistent with the observation that the drug treatment was effective only in the younger brother, despite the twin being genetically identical...
February 6, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28184925/inhibiting-plk1-induces-autophagy-of-acute-myeloid-leukemia-cells-via-mammalian-target-of-rapamycin-pathway-dephosphorylation
#8
Yan-Fang Tao, Zhi-Heng Li, Wei-Wei Du, Li-Xiao Xu, Jun-Li Ren, Xiao-Lu Li, Fang Fang, Yi Xie, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Gang Li, Yi Wu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, Jun Lu, Jian Pan
Decreased autophagy is accompanied by the development of a myeloproliferative state or acute myeloid leukemia (AML). AML cells are often sensitive to autophagy‑inducing stimuli, prompting the idea that targeting autophagy can be useful in AML cytotoxic therapy. AML NB4 cells overexpressing microtubule-associated protein 1 light chain 3-green fluorescent protein were screened with 69 inhibitors to analyze autophagy activity. AML cells were treated with the polo-like kinase 1 (PLK1) inhibitors RO3280 and BI2536 before autophagy analysis...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28182037/janus-kinase-2-mutations-in-cases-with-bcr-abl-negative-chronic-myeloproliferative-disorders-from-turkey
#9
Ismail Yildiz, Osman Yokuş, Habip Gedik
OBJECTIVE: We aimed to investigate the frequency of Janus kinase 2 (JAK2) mutations in cases with chronic myeloproliferative disorders (CMDs), and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively. MATERIALS AND METHODS: Patients, who were diagnosed with BCR-ABL-negative CMDs according to diagnosis criteria of the World Health Organization and followed up at the hematology clinic between 2013 and 2015, were investigated in terms of the frequency of JAK2 mutation in cases with CMDs, and the relationship between the presence of JAK2 mutation and leukocytosis and splenomegaly, retrospectively...
January 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28179280/gata-factor-mutations-in-hematologic-disease
#10
John D Crispino, Marshall S Horwitz
GATA family proteins play essential roles in development of many cell types, including hematopoietic, cardiac, and endodermal lineages. The first three factors, GATAs 1,2 and 3, are essential for normal hematopoiesis, and their mutations are responsible for a variety of blood disorders. Acquired and inherited GATA1 mutations contribute to Diamond Blackfan anemia, acute megakaryoblastic leukemia, transient myeloproliferative disorder and a group of related congenital dyserythropoietic anemias with thrombocytopenia...
February 8, 2017: Blood
https://www.readbyqxmd.com/read/28168700/progenitor-genotyping-reveals-a-complex-clonal-architecture-in-a-subset-of-calr-mutated-myeloproliferative-neoplasms
#11
Sarah Martin, Casey M Wright, Linda M Scott
The identification of acquired CALR mutations in patients with essential thrombocythaemia (ET) or myelofibrosis (MF) has meant that disease-initiating mutations can now be detected in about 90% of all patients with a myeloproliferative neoplasm (MPN). Here, we show that only those CALR mutations that cause a +1 frameshift, thereby altering the carboxy-terminus of calreticulin, promote cytokine independence in vitro; in-frame deletions were not functional, and are unlikely to be the pathogenetic mutation underlying some MPN cases...
February 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28167129/jak-stat-signaling-in-the-therapeutic-landscape-of-myeloproliferative-neoplasms
#12
Jennifer M O'Sullivan, Claire N Harrison
Myeloproliferative neoplasms (MPN) are a group of disorders defined by clonal proliferation of mature myeloid cells with overlapping clinical features. The driver mutations of these disorders, namely JAK2 (Janus Kinase), MPL (Myeloproliferative Leukaemia Virus) and CALR (Calreticulin) upregulate JAK-STAT signaling with increase in downstream transcription and gene expression. Epigenetic mutations are prevalent in MPNs but their interplay with aberrant JAK-STAT signaling is not known. This understanding lead to development of first targeted treatment in MPN; ruxolitinib for primary myelofibrosis...
February 3, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28164603/study-on-the-clinical-significance-of-jak2v617f-allele-burden-in-philadelphia-chromosome-negative-myeloproliferative-neoplasm
#13
Peisong Chen, Juan Ouyang, Jianming Liang, Xuegao Yu, Bin Huang
BACKGROUND: It was discovered that the somatic mutation in JAK2 exon 14 (JAK2V617F) totally modified the understanding and diagnosis of Philadelphia-Negative myeloproliferative neoplasm (Ph-MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Real-time quantitative PCR is the most widely used method for JAK2V617F detection in clinical laboratory. In this study, we aimed to evaluate the clinical significance of JAK2V617F allele burden in Ph-MPNs detected by real-time quantitative PCR...
August 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28161773/clinicopathological-differences-exist-between-calr-and-jak2-mutated-myeloproliferative-neoplasms-despite-a-similar-molecular-landscape-data-from-targeted-next-generation-sequencing-in-the-diagnostic-laboratory
#14
Rishu Agarwal, Piers Blombery, Michelle McBean, Kate Jones, Andrew Fellowes, Ken Doig, Cecily Forsyth, David A Westerman
Mutations in CALR have recently been detected in JAK2-negative myeloproliferative neoplasms (MPNs) and are key pathological drivers in these diseases. CALR-mutated MPNs are shown to have numerous clinicopathological differences to JAK2-mutated MPNs. The basis of these differences is poorly understood. It is unknown whether these differences result directly from any differences in intracellular signalling abnormalities induced by JAK2/CALR mutations or whether they relate to other phenomena such as a differing spectrum of genetic lesions between the two groups...
February 4, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28159760/nad-p-h-quinone-oxidoreductase-1-nqo1-competes-with-20s-proteasome-for-binding-with-c-ebp%C3%AE-leading-to-its-stabilization-and-protection-against-radiation-induced-myeloproliferative-disease
#15
https://www.readbyqxmd.com/read/28159740/the-chronic-myeloid-leukemia-stem-cell-stemming-the-tide-of-persistence
#16
Tessa L Holyoake, David Vetrie
Chronic myeloid leukaemia (CML) is caused by the acquisition of the tyrosine kinase BCR-ABL1 in a haemopoietic stem cell (HSC), transforming it into a leukaemic stem cell (LSC) that self-renews, proliferates and differentiates to give rise to a myeloproliferative disease. While tyrosine kinase inhibitors (TKI) that target the kinase activity of BCR-ABL1 have transformed CML from a once fatal disease to a manageable one for the vast majority of patients, only ~10% of those who present in chronic phase (CP) can discontinue TKI treatment and maintain a therapy-free remission...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28159736/myeloproliferative-neoplasm-stem-cells
#17
Adam J Mead, Ann Mullally
Myeloproliferative neoplasms (MPN) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provide a selective advantage to mutant HSC over normal HSC and promote myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiate and sustain MPN, are termed MPN stem cells. In greater than 95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in one of three genes: JAK2, CALR or MPL The thrombopoietin receptor, MPL is the key cytokine receptor in MPN development and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28159735/the-microenvironment-in-human-myeloid-malignancies-emerging-concepts-and-therapeutic-implications
#18
Hind Medyouf
Similar to their healthy counterpart, malignant hematopoietic stem cells in myeloid malignancies such as myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), reside in a highly complex and dynamic cellular microenvironment in the bone marrow. This environment provides key regulatory signals for and tightly controls cardinal features of HSCs, including self-renewal, quiescence, differentiation and migration. These features are essential to maintaining cellular homeostasis and blood regeneration throughout life...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28157219/the-role-of-the-extracellular-matrix-in-primary-myelofibrosis
#19
REVIEW
O Leiva, S K Ng, S Chitalia, A Balduini, S Matsuura, K Ravid
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that arises from clonal proliferation of hematopoietic stem cells and leads to progressive bone marrow (BM) fibrosis. While cellular mutations involved in the development of PMF have been heavily investigated, noteworthy is the important role the extracellular matrix (ECM) plays in the progression of BM fibrosis. This review surveys ECM proteins contributors of PMF, and highlights how better understanding of the control of the ECM within the BM niche may lead to combined therapeutic options in PMF...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28155840/osteitis-in-the-course-of-pyodema-gangrenosum-case-raport
#20
Andrzej Kaźmierczak-Koćwin, Robert Pieczyrak, Damian Kusz, Eugeniusz Kucharz, Marcin Kusz
We present the case of a male patient admitted to the Department of Orthopaedics and Musculoskeletal Traumatology, Medical University of Silesia (MUS) in Katowice, due to a right hindfoot abscess with calcaneal infiltration and pain in the forehead and the back, with evidence of local inflammation. The patient had a history of ulcerative colitis and sclerosing cholangitis was suspected. During the hospital stay, the patient underwent calcaneal CT, surgery (resection of an inflammatory focus) and MRI of the thoracic and lumbosacral spine, which revealed inflamed spinous processes of the Th10, Th11 and Th12 vertebrae...
November 30, 2016: Ortopedia, Traumatologia, Rehabilitacja
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