The t(11;14)(q13;32) is a common chromosome translocation in multiple myeloma (MM), but its prognostic value remains controversial. Immunoglobulin light chain amyloidosis is commonly secondary to multiple myeloma, which can rapidly cause heart failure and high mortality. We aimed to investigate the prevalence of secondary cardiac amyloidosis in MM patients with t(11;14) and to evaluate its impact on survival outcomes.We retrospectively identified 52 MM patients with t(11;14) in our center between October 2015 and April 2022. The associations between cardiac amyloidosis and clinical and biological parameters were statistically analyzed, and the impacts of concomitant of cardiac amyloidosis on survival and prognosis of MM patients with t(11;14) were also assessed.Concomitant presence of cardiac amyloidosis was observed in 15 (28.8%) of all cases. Patients with cardiac amyloidosis had significantly higher NT-proBNP (p = 0.002) and higher hs-cTnT (p < 0.001), while the patients without cardiac amyloidosis had higher percentage of bone marrow plasma cells (p = 0.027), higher incidence of hemoglobin <80 g/L (p = 0.021) and bone destruction (p < 0.001). The median overall survival (OS) for all patients was 33.4 months after a median follow-up of 23.8 months. The amyloidosis group showed a significantly shorter OS than the non-amyloidosis group (15.3 vs. 41.8 months, p < 0.001). Besides, patients harboring NT-proBNP >1,800 pg/ml (p < 0.001) or hs-cTnT ≧40 pg/ml (p = 0.001) or light chain (LC) only isotype (p = 0.033) had a significantly shorter mean OS compared with patients with lower NT-proBNP or hs-cTnT or other M-protein isotype. Univariate analyses showed that NT-proBNP >1,800 pg/ml, hs-cTnT ≧40 pg/ml, LC only isotype, and concomitant presence of cardiac amyloidosis were independently associated with shorter OS, while NT-proBNP >1,800 pg/ml still retained the prognostic value for OS in multivariate analyses.The t(11;14) MM patients with coexisting cardiac amyloidosis may represent a distinct clinical entity that confers a poor outcome. These findings may have important clinical and biological implications.
Previous study showed that downregulated BCL11B expression in T cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4 inhibited cell proliferation and induce apoptosis, which may be related to PHTF1 gene overexpression. The objective of this study was to investigate the expression of PHTF1 and related genes in ALL and further explore its function in T-ALL cell lines.Real-time PCR was used to determine the gene expression level of PHTF1 in hematologic malignancies. The PHTF1, BCL11B, FEM1B and Apaf-1 gene expression levels and correlations were analyzed in patients with primary ALL (including T-ALL and B-ALL) and healthy individuals (HIs). Inhibition and overexpression of PHTF1 by lentiviral transduction were performed using the Molt-4 and Jurkat cell lines. Cell growth and apoptosis were measured by the Cell Counting Kit-8 assay and flow cytometry, respectively. Upon PHTF1 overexpression, the BCL11B, FEM1B and Apaf-1 gene expression levels were determined by real-time PCR.PHTF1 overexpression was found in both T-ALL (p = 0.004) and B-ALL (p < 0.001) groups compared with HIs group. A trend toward a negative correlation between the PHTF1 and BCL11B genes was detected for the T-ALL group, while positively correlated expression was found for the PHTF1 and BCL11B genes in HIs (P = 0.001). FEM1b and Apaf-1 overexpression was found in recently diagnosed ALL patients compared with HIs (p < 0.05). Positively correlated expression was found for the PHTF1, FEM1b and Apaf-1 genes in patients with ALL (p < 0.05) and HIs (p < 0.05). Direct up-regulation of PHTF1 expression inhibited the proliferation of Jurkat and Molt-4 cells and effectively induced apoptosis in Molt-4 cells. Direct inhibition of PHTF1 expression had no significant effect on the proliferation or apoptosis of Jurkat and Molt-4 cells. FEM1b and Apaf-1 overexpression, which did not obviously alter the BCL11B expression level, was detected in PHTF1-transduced T-ALL cell lines.PHTF1 overexpression is responsible for regulating cell proliferation and apoptosis in T-ALL cell lines. PHTF1 may be a tumor-suppressor like gene and a therapeutic target for triggering the PHTF1-FEM1b-Apaf-1 apoptosis pathway.
A 13-year-old girl suddenly developed hypertrophic rough-surfaced plaques on both elbows, knees and ankles without obvious precipitating factors at 3 years of age. Because there was no subjective symptom or other discomfort, no treatment was given. Thereafter, the lesions neither faded nor spread. Skin examination revealed lesions covered with 1-2 mm-sized keratotic papules on the elbows and knees, which were clustered together and confluent in some areas. Circular keratotic plaques were observed on the ankles. Histopathology showed epidermal hyperkeratosis with mild parakeratosis, follicular keratotic plugs, acanthosis, broadened dermal papillae, telangiectasis and perivascular mononuclear infiltration in dermal papillae, infiltration of a few nonspecific cells in the superficial dermis. According to the clinical manifestations and histopathological findings, the patient was diagnosed with keratosis circumscripta, and treated with oral vitamin A and topical halometasone cream and urea-vitamin E cream. The degree of skin hypertrophy and roughness was decreased after 15 days of treatment, but increased 1 month after drug withdrawal.
Key words:
Keratosis; Skin manifestations; Pathological processes; Treatment outcome; Keratosis circumscripta
This paper states the sex,onset age,marriage,nationality course,occupation,lesion site,lesion area distribution of lesion,stage.family history,complication,related cause,past history,laboratory examination and therapy of 1 779 cases of Vitiligo.
Abstract Hypomethylating agents (HMAs) including azacitidine (AZA) represent the only FDA-approved first-line treatments for patients with chronic myelomonocytic leukemia (CMML). However, the mechanism by which HMAs produce therapeutic responses (e.g., hematological improvement) remains unclear. Bone marrow mesenchymal stromal cells (MSCs) play a crucial role in regulating the self-renewal, survival and differentiation of hematopoietic stem and progenitor cells (HSPCs). Recently, the identified sensitivity of patient-derived MSCs to HMAs underlines a critical yet unexplored role of MSCs in regulating post-HMA efficacies. By utilizing high-throughput approaches including targeted exon sequencing, DNA methylation profiling, and RNA sequencing, our present study aims to delineate the modifications and consequences of AZA on CMML-MSCs. Demonstrated by integrated multi-omics analysis, our results reveal that cytogenetically independent CMML-MSCs exhibit strikingly high amenability to AZA. Through selectively de-methylating/methylating CpGs of 1395 sensitive genes, AZA re-activates HSPC-supportive signatures and enhances the protective effect of CMML-MSCs on healthy HSPCs. Along with the reconstitution of the dysregulated methylome/transcriptome, AZA partially restored the impaired functions of CMML-MSCs to support healthy hematopoiesis in long-term co-culture conditions. Our findings suggested a niche-dependent mechanism of post-HMA recovery of normal hematopoiesis. Identifying AZA-sensitive genes and functions may be of particular value in developing niche-targeting strategies in treating myeloid malignancies.
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