RESUMEN
Myelodysplastic syndrome (MDS) represents a group of neoplasms with extensive heterogeneity. Recurrent mutations in dozens of driver genes have been identified in over 90% of MDS cases, although fusion genes are rarely seen. We first report the competitive evolved sub-clonal breakpoint cluster region (BCR)::ABL1 and novel MSI2::PC fusion gene in MDS with del(5q) in initial diagnosis that underwent dismal progression. However, the BCR::ABL1 clone vanished while the MSI2::PC clone rose to the major one with disease progression. A novel MSI2::PC fusion transcript was identified in initial diagnosis and disease progression of the patient through transcriptome sequencing (RNA-seq) and Quantitative reverse transcription polymerase Chain Reaction (PCR) showed MSI2::PC/ABL1 expression at initial diagnosis and disease progression. In addition, mutation screening of 300 leukemia driver genes identified ARID2 c.5046del/p.F1682Lfs*19 and ZNF292 c.4565A > G/p.Q1522R mutation in bone marrow sample at initial diagnosis and disease progression. In conclusion, the dynamic process of the two fusion and phenotype manifestations may help to understand further the molecular significance of the anomalies of BCR::ABL1, MSI2, and PC in oncogenesis.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Síndromes Mielodisplásicos , Humanos , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Síndromes Mielodisplásicos/genética , Mutación , Progresión de la Enfermedad , Proteínas de Unión al ARN/genética , Proteínas Portadoras/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
Several cases such as myeloproliferative neoplasms (MPN) with the coexistence of JAK2 and BCR-ABL have been reported. However, cases of transformation of essential thrombocythemia (ET) into chronic myeloid leukemia (CML) during the disease progression were rarely reported. Here, we report the case of a patient with JAK2 V617F- positive ET who subsequently acquired BCR-ABL1, which transformed the disease into CML after 10 years from the initial diagnosis. In this study, we dynamically monitored JAK2 V617F and BCR-ABL and observed multiple gene mutations, including IDH2, IDH1, ASXL1, KRAS, and RUNX1. It is important to be aware of this potentially clone evolution in disease progression.
RESUMEN
Background: Lumbar spondylolisthesis is a common clinical spinal lesion. The upper vertebral body of the patient is displaced relative to the lower vertebral body, causing spinal instability and nerve compression. The clinical manifestations are low back and leg pain, abnormal lower limb sensation, and intermittent rupture. In severe cases, cauda equina syndrome and paraplegia may occur. Minimally invasive spinal surgery has developed rapidly in recent years and become the preferred treatment for lumbar spondylolisthesis. Objective: The aim of this study is to investigate the clinical effect of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) combined with percutaneous pedicle screw fixation in the treatment of lumbar spondylolisthesis under microscope. Methods: The clinical and surgical data of 106 patients with lumbar spondylolisthesis treated in our hospital were selected and divided into research group (56 cases) according to surgical methods (MIS-TLIF combined with percutaneous pedicle screw fixation). The other 50 patients were treated with traditional open percutaneous intervertebral foramen fusion (control group). The surgical trauma-related indicators, visual analog pain scale (VAS) scores before and after surgery, modified Japanese Orthopedic Association low back pain score (JOA), bone graft fusion effect, spinal pelvic parameters, and surgical complications of the two groups were statistically analyzed in detail. Results: The incision length, intraoperative blood loss, operation time, and hospitalization time in the research group were lower than those in the control group, and the differences were statistically significant (P < 0.05). There was no significant difference in the VAS score and JOA score between the two groups before operation (P > 0.05). The VAS score and JOA score of the research group were lower than those of the control group on the first day after operation (P < 0.05). There was no significant difference in the VAS score and JOA score between the two groups at 1 month and 3 months after operation (P > 0.05). Six months, 12 months, and 18 months after operation, the bone graft fusion rates in the research group were 42.86%, 73.21%, and 94.64%, respectively, and those in the control group were 40.00%, 68.00%, and 92.00%, respectively, with no significant difference (P > 0.05). There was no significant difference in PI, PT, SS, LL, TK, LSJA, and SVA between the two groups before and 6 months after operation (P > 0.05). At 6 months after operation, the PT and TK values of the two groups were higher than those before operation (P < 0.05), and the SS, LL, LSJA, and SVA values of the two groups were lower than those before operation (P < 0.05). The complication rate of the research group was 3.57%, which was lower than 18.00% of the control group, and the difference was statistically significant (P < 0.05). Conclusion: MIS-TLIF combined with percutaneous pedicle screw fixation in the treatment of lumbar spondylolisthesis has the same effect as traditional open surgery and has the same correction effect for spinal pelvic parameters, but it has the advantages of less trauma and fewer complications.
RESUMEN
Acute myocardial infarction (AMI) is a condition triggered by an inflammatory process that seriously affects human health. Calcium-sensing receptor (CaSR) in T lymphocytes is involved during the inflammation reaction. However, the relationship between them is not very clear. In this study, we collected human peripheral blood T lymphocytes from patients with AMI and in different stages of percutaneous coronary intervention (PCI) (at the onset of AMI, the first day after PCI (PCI-1), PCI-3, and PCI-5) to study the CaSR and NF-κB pathway protein expression, cytokine release and T cell apoptosis. The results showed that the expressions of CaSR, P-p65, Caspase-12, and the secretions of Th-1 and Th-2 type cytokines were increased at the onset of AMI, especially on the PCI-1. Meanwhile, the apoptosis rate of CD(3+), CD(4+) and CD(8+) T lymphocytes also increased. However, from PCI-3, all the indicators began to decline. In addition, we also found that positive CaSR small interfering RNA (siRNA) transfection in T lymphocytes and NF-κB pathway blocker Bay-11-7082 reversed the increased expressions of CaSR, P-p65, Caspase-12, reduced the secretions of Th-1 and Th-2 type cytokines, and decreased T lymphocytes apoptosis rate not only in the AMI patients but also in the normal controls. All of these results indicated that CaSR in the human peripheral blood T lymphocytes were involved in the AMI onset and progression, which probably was related to the NF-κB pathway. Our study demonstrated the relationship between AMI and CaSR, and will provide new effective prevention theory and new targets for drug treatment.
Asunto(s)
Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , FN-kappa B/metabolismo , Receptores Sensibles al Calcio/metabolismo , Linfocitos T/metabolismo , Animales , Apoptosis/fisiología , Caspasa 12/metabolismo , Femenino , Masculino , Estudios Prospectivos , Receptores Sensibles al Calcio/genética , Transducción de Señal/fisiologíaRESUMEN
Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca(2+) release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca(2+) imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca(2+) ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca(2+) imaging, we found that the depletion of ER Ca(2+) stores by TG elicited a transient rise in cytoplasmic Ca(2+), followed by sustained increase depending on extracellular Ca(2+). But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na(+)/Ca(2+) exchanger inhibitor), inhibited the relatively high [Ca(2+)]i. NPS R-568 also resulted in the same effect, and the duration of [Ca(2+)]i increase was eliminated completely by U73122 and was reduced in the absence of [Ca(2+)]o. NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis.