Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MΦs (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MΦs (MM-associated macrophages) have pro-myeloma functions, and BM MM-MΦs numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MΦs, which expressed higher BMI1 levels relative to normal MΦs. In the MM tumor microenvironment, hedgehog signaling in MΦs was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MΦs, BMI1-KO (BMI1 knockout) MM-MΦs from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MΦs lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MΦs, BMI1-KO MM-MΦs lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MΦs.

Multiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

Aim: This study aimed to investigate compassion satisfaction (CS) and compassion fatigue (CF) in haematology nurses and their associated factors.Design: A cross‐sectional survey.Methods: The survey was conducted on 336 haematology nurses from 21 hospitals in Sichuan, China. The CS and CF were assessed by the Professional Quality of Life Scale version 5. The CF was determined by burnout and secondary traumatic stress.Results: Haematology nurses in China had moderate levels of CS and moderate‐to‐low CF. Better nursing competence of teaching/consultation and communication/coordination and the percentage of critically ill patients >60% predicted higher CS. The permanent nurse, better nursing competence of communication/coordination and specialized clinical practice predicted less burnout, while working >40 hr per week or more nurse‐patient conflict events predicted more burnout. In addition, working >40 hr per week, more nurse‐patient conflict events and having the need of psychological support predicted higher secondary traumatic stress.

Background: Adult acute leukemia (AL) patients who receive chemotherapy usually experience multiple symptoms during the treatment course. The symptom clusters (SCs) as well as subsets of concurrent symptoms in AL patients have not yet been demonstrated. Objective: To investigate the SCs of adult AL patients who were receiving chemotherapy and to determine their correlations with functional performance. Methods: A total of 132 hospitalized adult AL patients were included in this study. A cross-sectional survey aimed to examine symptoms and functional performance was conducted. The patients’ symptoms were assessed using the Chinese version of the Condensed Memorial Symptom Assessment Scale, and functional performance was evaluated through activities of daily living and quality of life. Results: We identified 4 SCs in adult AL patients: psychological SC, pain-fatigue-sleep SC, dry mouth–constipation SC, and nutrition-impaired SC. The psychological SC was the most common and most distressing SC. The different SCs were each differentially correlated with patient characteristics. The distress of the psychological SC, pain-fatigue-sleep SC, and nutrition-impaired SC was adversely correlated with functional performance. Conclusions: Adult AL patients undergoing chemotherapy experience multiple symptoms that can be further categorized into 4 SCs. The distress from some SCs is negatively associated with patients’ functional performance. Implications for Practice: Symptom burden remains a major problem for adult AL patients undergoing chemotherapy. Identifying SCs of AL patients should be the basis for accurate and cost-effective interventions. Personalized SC management may improve the functional performance and healthcare quality of adult AL patients.

Our previous data showed that young female multiple myeloma (MM) patients had a low frequency of osteolytic lesions. Based on this clinical observation, we found that estrogen cell signaling played a regulatory role in MM bone disease (MMBD), and the estrogen-responsive gene microtubule-associated serine/threonine kinase family member 4 (MAST4) was a critical factor. The presence of estrogen in cell cultures promoted MAST4 expression in MM cells while knocking down estrogen receptor 1 (ESR1) inhibited MAST4 expression. Chromatin immunoprecipitation assay suggested a binding site of ESR1 on the MAST4 promoter. Bisphosphonates, such as zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate MAST4 expression in MM cells by promoting ESR1 expression. MAST4 interacted with phosphatase and tensin homolog (PTEN), therefore regulating the PI3K-Akt-mTOR pathway and the expression of downstream cytokines, such as CCL2/3/4. MAST4 knockdown (MAST4-KD) or ESR1 knockdown (ESR1-KD) MM cells had repressed PTEN activity, elevated PI3K-Akt-mTOR activity and increased CCL2/3/4 expressions. Coculture of MAST4-KD or ESR1-KD MM cells with pre-osteoclasts (pre-OCs) stimulated OCs formation in vitro while neutralizing antibodies of CCL2/3/4 attenuated such stimulation. In mouse models, mice inoculated with MAST4-KD or ESR1-KD MM cells had severer MMBD than control knockdown (CTR-KD). The correlations between MAST4 and ESR1 expressions in MMBD, as well as related cell signaling pathways, were confirmed in analyses using gene expression profiles (GEPs) of patients’ MM cells. The negative correlation of MAST4 expression and occurrence of MMBD was further validated by patients’ immunohistochemical tissue array. Overall, our data suggested that estrogen cell signaling negatively regulated MMBD through MAST4.