Browsing by Subject "HEMATOPOIETIC STEM"

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  • Turunen, A; Silvennoinen, R; Partanen, A; Valtola, J; Siitonen, T; Putkonen, M; Sankelo, M; Pyorala, M; Kuittinen, T; Penttila, K; Sikio, A; Savolainen, ER; Mantymaa, P; Pelkonen, J; Varmavuo, V; Jantunen, E (2021)
    Background Autologous stem cell transplantation (auto-SCT) is a widely used treatment option in multiple myeloma (MM) patients. The optimal graft cellular composition is not known. Study design and methods Autograft cellular composition was analyzed after freezing by flow cytometry in 127 MM patients participating in a prospective multicenter study. The impact of graft cellular composition on hematologic recovery and outcome after auto-SCT was evaluated. Results A higher graft CD34(+) cell content predicted faster platelet recovery after auto-SCT in both the short and long term. In patients with standard-risk cytogenetics, a higher graft CD34(+) count (>2.5 x 10/kg) was linked with shorter progression-free survival (PFS; 28 vs. 46 months, p = 0.04), but there was no difference in overall survival (OS) (p = 0.53). In a multivariate model, a higher graft CD34(+)CD133(+)CD38(-) (>0.065 x 10/kg, p = 0.009) and NK cell count (>2.5 x 10/kg, p = 0.026), lenalidomide maintenance and standard-risk cytogenetics predicted better PFS. In contrast, a higher CD34(+) count (>2.5 x 10/kg, p = 0.015) predicted worse PFS. A very low CD3(+) cell count ( Conclusions Autograft cellular composition may impact outcome in MM patients after auto-SCT. More studies are needed to define optimal graft composition.
  • Turunen, Antti; Partanen, Anu; Valtola, Jaakko; Ropponen, Antti; Siitonen, Timo; Kuittinen, Outi; Kuitunen, Hanne; Putkonen, Mervi; Sankelo, Marja; Keskinen, Leena; Savolainen, Eeva-Riitta; Pyörälä, Marja; Kuittinen, Taru; Silvennoinen, Raija; Penttilä, Karri; Sikiö, Anu; Vasala, Kaija; Mäntymaa, Pentti; Pelkonen, Jukka; Varmavuo, Ville; Jantunen, Esa (2020)
    BACKGROUND Autologous stem cell transplantation is an established treatment option for patients with multiple myeloma (MM) or non-Hodgkin?s lymphoma (NHL). STUDY DESIGN AND METHODS In this prospective multicenter study, 147 patients with MM were compared with 136 patients with NHL regarding the mobilization and apheresis of blood CD34+ cells, cellular composition of infused blood grafts, posttransplant recovery, and outcome. RESULTS Multiple myeloma patients mobilized CD34+ cells more effectively (6.3???106/kg vs. 3.9???106/kg, p?=?0.001). The proportion of poor mobilizers (peak blood CD34+ cell count 100?days) nonrelapse mortality (NRM; 6% vs. 0%, p?=?0.003). CONCLUSIONS Non-Hodgkin?s lymphoma and MM patients differ in terms of mobilization of CD34+ cells, graft cellular composition, and posttransplant recovery. Thus, the optimal graft characteristics may also be different.
  • Lengefeld, Jette; Cheng, Chia-Wei; Maretich, Pema; Blair, Marguerite; Hagen, Hannah; McReynolds, Melanie R.; Sullivan, Emily; Majors, Kyra; Roberts, Christina; Kang, Joon Ho; Steiner, Joachim D.; Miettinen, Teemu P.; Manalis, Scott R.; Antebi, Adam; Morrison, Sean J.; Lees, Jacqueline A.; Boyer, Laurie A.; Yilmaz, Ömer H.; Amon, Angelika (2021)
    Stem cells are remarkably small. Whether small size is important for stem cell function is unknown. We find that hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferation and was accompanied by altered metabolism. Preventing HSC enlargement or reducing large HSCs in size averts the loss of stem cell potential under conditions causing stem cell exhaustion. Last, we show that murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function in vivo and propose that stem cell enlargement contributes to their functional decline during aging.
  • Sarin, Heikki V.; Gudelj, Ivan; Honkanen, Jarno; Ihalainen, Johanna K.; Vuorela, Arja; Lee, Joseph H.; Jin, Zhenzhen; Terwilliger, Joseph D.; Isola, Ville; Ahtiainen, Juha P.; Häkkinen, Keijo; Juric, Julija; Lauc, Gordan; Kristiansson, Kati; Hulmi, Juha J.; Perola, Markus (2019)
    Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate
  • Rodriguez, Alfredo; Zhang, Kaiyang; Färkkilä, Anniina; Filiatrault, Jessica; Yang, Chunyu; Velazquez, Martha; Furutani, Elissa; Goldman, Devorah C.; Garcia de Teresa, Benilde; Garza-Mayen, Gilda; McQueen, Kelsey; Sambel, Larissa A.; Molina, Bertha; Torres, Leda; Gonzalez, Marisol; Vadillo, Eduardo; Pelayo, Rosana; Fleming, William H.; Grompe, Markus; Shimamura, Akiko; Hautaniemi, Sampsa; Greenberger, Joel; Frias, Sara; Parmar, Kalindi; D'Andrea, Alan D. (2021)
    Bone marrow failure (BMF) in Fanconi anemia (FA) patients results from dysfunctional hematopoietic stem and progenitor cells (HSPCs). To identify determinants of BMF, we performed single-cell transcriptome profiling of primary HSPCs from FA patients. In addition to overexpression of p53 and TGF-beta pathway genes, we identified high levels of MYC expression. We correspondingly observed coexistence of distinct HSPC subpopulations expressing high levels of TP53 or MYC in FA bone marrow (BM). Inhibiting MYC expression with the BET bromodomain inhibitor (+)-JQ1 reduced the clonogenic potential of FA patient HSPCs but rescued physiological and genotoxic stress in HSPCs from FA mice, showing that MYC promotes proliferation while increasing DNA damage. MYC-high HSPCs showed significant downregulation of cell adhesion genes, consistent with enhanced egress of FA HSPCs from bone marrow to peripheral blood. We speculate that MYC overexpression impairs HSPC function in FA patients and contributes to exhaustion in FA bone marrow.