Abstract. Myeloproliferative neoplasms (MPNs) result from the malignant transformation of a hematopoietic stem-cell (HSC), leading to abnormal amplification and proliferation of myeloid lineages. Identification of the Janus kinase 2 (JAK2) V617F mutation developed the knowledge of Philadelphia-negative (PN)-MPNs, contributing to and influencing the definition of the phenotype and prognostic impact. Considering the lack of Portuguese epidemiological data, the present study intends to characterize the prevalence of the JAK2 mutation in a PN-MPN versus a control Portuguese population. Caucasian Portuguese PN-MPN patients (n=133) and 281 matched control subjects were investigated. No significant differences were identified between the case and control groups concerning age distribution or smoking habits. Pathology distribution was as follows: 60.2% with essential thrombocythemia (ET), 29.3% with polycythemia vera (PV) and 10.5% with primary myelofibrosis (PMF). A total of 75.0% of patients were positive for the presence of the JAK2 V617F mutation. In addition, the prevalence of PV was 87.2%, ET was 73.4% and PMF was 50.0%. The JAK2 V617F mutation is observed in various MPN phenotypes, and has an increased incidence in ET patients and a decreased incidence in PV patients. These data may contribute to improving the knowledge of the pathophysiology of these disorders, and to a more rational and efficient selection of therapeutic strategies to be adopted, notably because most of the patients are JAK2 V617F negative.

Stroke is an example of neurological diseases that can commonly drives Excessive Daytime Sleepiness (EDS). Extensive strokes with brain edema can leave a brain herniation and coma. Other causes of EDS after stroke are strategic lesions at Thalamus and brainstein. A 56-year-old man, right handed, with hypertension and hypercholesterolemia was admitted at Emergency Room due to 5 days onset of EDS, memory impairment, and left-sided weakness. A brain magnetic resonance imaging showed paramedian thalamic hyperintensity with rostral midbrain hyperintensity extending along the pial surface of the interpeduncular fossa. The artery of Percheron (AP) is an unusual anatomical variation that originates from the posterior cerebral artery and irrigates the paramedian regions of the thalamus and part of the midbrain. It is important the clinical suspicions with detailed drowsy patients history. Awareness of the clinical and neuroimaging features of this stroke syndrome is essential for timely diagnosis and appropriate management.

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The role of base excision repair (BER) genes in Philadelphia-negative (PN)-myeloproliferative neoplasms (MPNs) susceptibility was evaluated by genotyping eight polymorphisms [apurinic/apyrimidinic endodeoxyribonuclease 1, mutY DNA glycosylase, earlier mutY homolog (E. coli) (MUTYH), 8-oxoguanine DNA glycosylase 1, poly (ADP-ribose) polymerase (PARP) 1, PARP4 and X-ray repair cross-complementing 1 (XRCC1)] in a case-control study involving 133 Caucasian Portuguese patients. The results did not reveal a correlation between individual BER polymorphisms and PN-MPNs when considered as a whole. However, stratification for essential thrombocythaemia revealed i) borderline effect/tendency to increased risk when carrying at least one variant allele for XRCC1_399 single-nucleotide polymorphism (SNP); ii) decreased risk for Janus kinase 2-positive patients carrying at least one variant allele for XRCC1_399 SNP; and iii) decreased risk in females carrying at least one variant allele for MUTYH SNP. Combination of alleles demonstrated an increased risk to PN-MPNs for one specific haplogroup. These findings may provide evidence for gene variants in susceptibility to MPNs. Indeed, common variants in DNA repair genes may hamper the capacity to repair DNA, thus increasing cancer susceptibility.

Introduction:The identification of BCR-ABL expression as the defining leukemogenic event in chronic myeloid leukemia (CML) and the introduction of BCR-ABL tyrosine kinase inhibitors in 2001 have revolutionized disease management, leading to a reduction in mortality rates and accordingly an increase in the estimated prevalence of CML.Case report:Based on medical records and clinical follow-up, the authors present the case of a Philadelphia chromosome–positive CML patient who developed resistance to imatinib. Quantitative reverse transcription-polymerase chain reaction testing revealed a V280G BCR-ABL mutation.Discussion and conclusions:This is the first report describing a new BCR-ABL kinase domain mutation—V280G—that might be associated with resistance to imatinib. Approximately 15% to 30% of patients treated with imatinib discontinue treatment due to resistance or intolerance. More than 90 BCR-ABL mutations were detected so far, conferring variable degrees of drug resistance, with consequent clinical, therapeutic, and prognostic impact.