Role of bone marrow adipocytes in leukemia and chemotherapy challenges

  • Azin Samimi
  • Majid Ghanavat
  • Saeid Shahrabi
  • Shirin Azizidoost
  • Najmaldin SakiEmail author


Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia. Relevant literature was identified through a PubMed search (2000–2018) of English-language papers using the following terms: leukemia, adipocyte, leukemic stem cell, chemotherapy, and bone marrow. Findings suggest the striking interplay between leukemic cells and adipocytes to create a unique microenvironment supporting the metabolic demands and survival of leukemic cells. Based on these findings, targeting lipid metabolism of leukemic cells and adipocytes in combination with standard therapeutic agents might present novel treatment options.


Adipocyte Leukemia Leukemic stem cell Chemotherapy Bone marrow 


Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, informed consent is not required.


  1. 1.
    Askmyr M, Quach J, Purton LE (2011) Effects of the bone marrow microenvironment on hematopoietic malignancy. Bone 48(1):115–120Google Scholar
  2. 2.
    Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H et al (2014) Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab 20(2):368–375Google Scholar
  3. 3.
    Wöhrer S, Rabitsch W, Shehata M, Kondo R, Esterbauer H, Streubel B et al (2007) Mesenchymal stem cells in patients with chronic myelogenous leukaemia or bi-phenotypic Ph+ acute leukaemia are not related to the leukaemic clone. Anticancer Res 27(6):3837–3841Google Scholar
  4. 4.
    Hardaway AL, Herroon MK, Rajagurubandara E, Podgorski I (2014) Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases. Cancer Metastasis Rev 33(2–3):527–543Google Scholar
  5. 5.
    Fitter S, Vandyke K, Schultz CG, White D, Hughes TP, Zannettino AC (2010) Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: a mechanism for improved insulin sensitivity in type 2 diabetic CML patients? J Clin Endocrinol Metab 95(8):3763–3767Google Scholar
  6. 6.
    Johrer K, Ploner C, Thangavadivel S, Wuggenig P, Greil R (2015) Adipocyte-derived players in hematologic tumors: useful novel targets? Expert Opin Biol Ther 15(1):61–77Google Scholar
  7. 7.
    Lu W, Wan Y, Li Z, Zhu B, Yin C, Liu H et al (2018) Growth differentiation factor 15 contributes to marrow adipocyte remodeling in response to the growth of leukemic cells. J Exp Clin Cancer Res 66(1):37Google Scholar
  8. 8.
    Shafat MS, Oellerich T, Mohr S, Robinson SD, Edwards DR, Marlein CR et al (2017) Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood 129(10):1320–1332Google Scholar
  9. 9.
    Feldman BJ, Streeper RS, Farese RV, Yamamoto KR (2006) Myostatin modulates adipogenesis to generate adipocytes with favorable metabolic effects. Proc Natl Acad Sci USA 103(42):15675–15680Google Scholar
  10. 10.
    Tucci J, Sheng X, Mittelman SD (2014) Acute lymphoblastic leukemia cells stimulate adipocyte lipolysis and utilize adipocyte-derived free-fatty acids for proliferation. AACR. Google Scholar
  11. 11.
    Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K (2013) Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res 52(4):585–589Google Scholar
  12. 12.
    Lu W, Weng W, Zhu Q, Zhai Y, Wan Y, Liu H et al (2018) Small bone marrow adipocytes predict poor prognosis in acute myeloid leukemia. Haematologica. 103(1):e21–e24Google Scholar
  13. 13.
    Ambrosi TH, Scialdone A, Graja A, Gohlke S, Jank A-M, Bocian C et al (2017) Adipocyte accumulation in the bone marrow during obesity and aging impairs stem cell-based hematopoietic and bone regeneration. Cell Stem Cell 20(6):771–846Google Scholar
  14. 14.
    Scheller EL, Rosen CJ (2014) What’s the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Ann N Y Acad Sci 1311:14–30Google Scholar
  15. 15.
    Ohishi M, Schipani E (2010) Bone marrow mesenchymal stem cells. J Cell Biochem 109(2):277–282Google Scholar
  16. 16.
    Torii I, Morikawa S, Nakano A, Morikawa K (2003) Establishment of a human preadipose cell line, HPB-AML-I: Refractory to PPARγ-mediated adipogenic stimulation. J Cell Physiol 197(1):42–52Google Scholar
  17. 17.
    Falconi D, Oizumi K, Aubin JE (2007) Leukemia inhibitory factor influences the fate choice of mesenchymal progenitor cells. Stem Cells 25(2):305–312Google Scholar
  18. 18.
    Reiter SS, Halsey CH, Stronach BM, Bartosh JL, Owsley WF, Bergen WG (2007) Lipid metabolism related gene-expression profiling in liver, skeletal muscle and adipose tissue in crossbred Duroc and Pietrain pigs. Comp Biochem Physiol Part D 2(3):200–206Google Scholar
  19. 19.
    Vicente Lopez A, Vazquez Garcia MN, Melen GJ, Entrena Martinez A, Cubillo Moreno I, Garcia-Castro J et al (2014) Mesenchymal stromal cells derived from the bone marrow of acute lymphoblastic leukemia patients show altered BMP4 production: correlations with the course of disease. PLoS One 9(1):e84496Google Scholar
  20. 20.
    Ikeda S, Itoh S, Yamamoto Y, Yamauchi Y, Matsushita K, Naruse H et al (2016) Developmental stage-dependent effects of leukemia inhibitory factor on adipocyte differentiation of murine bone marrow stromal cells. Cell Biochem Biophys 74(1):11–17Google Scholar
  21. 21.
    Hogan JC, Stephens JM (2005) Effects of leukemia inhibitory factor on 3T3-L1 adipocytes. J Endocrinol 185(3):485–496Google Scholar
  22. 22.
    Chen X, Hausman BS, Luo G, Zhou G, Murakami S, Rubin J et al (2013) Protein kinase inhibitor gamma reciprocally regulates osteoblast and adipocyte differentiation by downregulating leukemia inhibitory factor. Stem Cells 31(12):2789–2799Google Scholar
  23. 23.
    Fox KE, Fankell DM, Erickson PF, Majka SM, Crossno JT Jr, Klemm DJ (2006) Depletion of cAMP-response element-binding protein/ATF1 inhibits adipogenic conversion of 3T3-L1 cells ectopically expressing CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBP beta, or PPAR gamma 2. J Biol Chem 281(52):40341–40353Google Scholar
  24. 24.
    Petersen RK, Madsen L, Pedersen LM, Hallenborg P, Hagland H, Viste K et al (2008) Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes. Mol Cell Biol 28(11):3804–3816Google Scholar
  25. 25.
    Li F, Wang D, Zhou Y, Zhou B, Yang Y, Chen H et al (2008) Protein kinase A suppresses the differentiation of 3T3-L1 preadipocytes. Cell Res 18(2):311–323Google Scholar
  26. 26.
    Li H, Fong C, Chen Y, Cai G, Yang M (2010) Beta-adrenergic signals regulate adipogenesis of mouse mesenchymal stem cells via cAMP/PKA pathway. Mol Cell Endocrinol 323(2):201–207Google Scholar
  27. 27.
    Battula VL, Chen Y, Cabreira Mda G, Ruvolo V, Wang Z, Ma W et al (2013) Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment. Blood 122(3):357–366Google Scholar
  28. 28.
    Battula VL, Le PM, Sun JC, Nguyen K, Yuan B, Zhou X et al (2017) AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth. JCI Insight 2:13Google Scholar
  29. 29.
    Boyd AL, Reid JC, Salci KR, Aslostovar L, Benoit YD, Shapovalova Z et al (2017) Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche. Nat Cell Biol 19(11):1336Google Scholar
  30. 30.
    Takam Kamga P, Bassi G, Cassaro A, Midolo M, Di Trapani M, Gatti A et al (2016) Notch signalling drives bone marrow stromal cell-mediated chemoresistance in acute myeloid leukemia. Oncotarget 7(16):21713–21727Google Scholar
  31. 31.
    Mattiucci D, Maurizi G, Izzi V, Cenci L, Ciarlantini M, Mancini S et al (2018) Bone marrow adipocytes support hematopoietic stem cell survival. J Cell Physiol 233(2):1500–1511Google Scholar
  32. 32.
    Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ (2009) Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 460(7252):259–263Google Scholar
  33. 33.
    Zhou BO, Yu H, Yue R, Zhao Z, Rios JJ, Naveiras O (2017) Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF. Nat Cell Biol 19(8):891–903Google Scholar
  34. 34.
    Veldhuis-Vlug AG, Rosen CJ (2018) Clinical implications of bone marrow adiposity. J Intern Med 283(2):121–139Google Scholar
  35. 35.
    Tabe Y, Yamamoto S, Saitoh K, Sekihara K, Monma N, Ikeo K et al (2017) Bone marrow adipocytes facilitate fatty acid oxidation activating AMPK and a transcriptional network supporting survival of acute monocytic leukemia cells. Cancer Res 77(6):1453–1464Google Scholar
  36. 36.
    Samudio I, Harmancey R, Fiegl M, Kantarjian H, Konopleva M, Korchin B et al (2010) Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 120(1):142–156Google Scholar
  37. 37.
    Perea G, Domingo A, Villamor N, Palacios C, Junca J, Torres P et al (2005) Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients. Leukemia Res 29(10):1109–1116Google Scholar
  38. 38.
    Ye H, Adane B, Khan N, Sullivan T, Minhajuddin M, Gasparetto M et al (2016) Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche. Cell Stem Cell 19(1):23–37Google Scholar
  39. 39.
    Frączak E, Olbromski M, Piotrowska A, Glatzel-Plucińska N, Dzięgiel P, Dybko J et al (2018) Bone marrow adipocytes in haematological malignancies. Acta Histochem 120(1):22–27Google Scholar
  40. 40.
    Caers J, Deleu S, Belaid Z, De Raeve H, Van Valckenborgh E, De Bruyne E et al (2007) Neighboring adipocytes participate in the bone marrow microenvironment of multiple myeloma cells. Leukemia 21(7):1580Google Scholar
  41. 41.
    Avcu F, Ural AU, Yilmaz MI, Bingol N, Nevruz O, Caglarc K (2006) Association of plasma adiponectin concentrations with chronic lymphocytic leukemia and myeloproliferative diseases. Int J Hematol 83(3):254–258Google Scholar
  42. 42.
    Jöhrer K, Ploner C, Thangavadivel S, Wuggenig P, Greil R (2015) Adipocyte-derived players in hematologic tumors: useful novel targets? Expert Opin Biol Therss 15(1):61–77Google Scholar
  43. 43.
    Petridou E, Mantzoros C, Dessypris N, Dikalioti S, Trichopoulos D (2006) Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer 94(1):156Google Scholar
  44. 44.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N et al (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96(5):1723–1732Google Scholar
  45. 45.
    Yamauchi T, Kamon J, Ya Minokoshi, Ito Y, Waki H, Uchida S et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8(11):1288Google Scholar
  46. 46.
    Medina E, Oberheu K, Polusani S, Ortega V, Velagaleti G, Oyajobi B (2014) PKA/AMPK signaling in relation to adiponectin’s antiproliferative effect on multiple myeloma cells. Leukemia 28(10):2080–2089Google Scholar
  47. 47.
    Dalamaga M, Karmaniolas K, Panagiotou A, Hsi A, Chamberland J, Dimas C et al (2009) Low circulating adiponectin and resistin, but not leptin, levels are associated with multiple myeloma risk: a case-control study. Cancer Causes Control 20(2):9–193Google Scholar
  48. 48.
    Kelesidis I, Kelesidis T, Mantzoros CS (2006) Adiponectin and cancer: a systematic review. Br J Cancer 94(9):1221–1225Google Scholar
  49. 49.
    Han TJ, Wang X (2015) Leptin and its receptor in hematologic malignancies. Int J Clin Exp Med 8(11):19840–19849Google Scholar
  50. 50.
    Hino M, Nakao T, Yamane T, Ohta K, Takubo T, Tatsumi N (2000) Leptin receptor and leukemia. Leuk Lymphoma 36(5–6):457–461Google Scholar
  51. 51.
    Kohler J, Moon R, Wright S, Willows E, Davies J (2011) Increased adiposity and altered adipocyte function in female survivors of childhood acute lymphoblastic leukaemia treated without cranial radiation. Horm Res Paediatr 75(6):433–440Google Scholar
  52. 52.
    Tabe Y, Konopleva M, Munsell MF, Marini FC, Zompetta C, McQueen T et al (2004) PML-RARα is associated with leptin-receptor induction: the role of mesenchymal stem cell–derived adipocytes in APL cell survival. Blood 103(5):1815–1822Google Scholar
  53. 53.
    Foss B, Mentzoni L, Bruserud O (2001) Effects of vascular endothelial growth factor on acute myelogenous leukemia blasts. J Hematother Stem Cell Res℃ 10(1):81–93Google Scholar
  54. 54.
    Gorska E, Popko K, Wasik M (2013) Leptin receptor in childhood acute leukemias. Adv Exp Med Biol 756:155–161Google Scholar
  55. 55.
    Juarez J, Bradstock KF, Gottlieb DJ, Bendall LJ (2003) Effects of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia 17(7):1294–1300Google Scholar
  56. 56.
    Hosokawa Y, Hosokawa I, Ozaki K, Nakae H, Murakami K, Miyake Y et al (2005) CXCL12 and CXCR4 expression by human gingival fibroblasts in periodontal disease. Clin Exp Immunol 141(3):467–474Google Scholar
  57. 57.
    Diaz-Blanco E, Bruns I, Neumann F, Fischer JC, Graef T, Rosskopf M et al (2007) Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase. Leukemia 21(3):494–504Google Scholar
  58. 58.
    Beaulieu A, Poncin G, Belaid-Choucair Z, Humblet C, Bogdanovic G, Lognay G et al (2011) Leptin reverts pro-apoptotic and antiproliferative effects of α-linolenic acids in BCR-ABL positive leukemic cells: involvement of PI3K pathway. PLoS One 6(10):e25651Google Scholar
  59. 59.
    Mouzaki A, Panagoulias I, Dervilli Z, Zolota V, Spadidea P, Rodi M et al (2009) Expression patterns of leptin receptor (OB-R) isoforms and direct in vitro effects of recombinant leptin on OB-R, leptin expression and cytokine secretion by human hematopoietic malignant cells. Cytokine 48(3):203–211Google Scholar
  60. 60.
    Jones RG, Thompson CB (2009) Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 23(5):537–548Google Scholar
  61. 61.
    Sheng X, Mittelman SD (2014) The role of adipose tissue and obesity in causing treatment resistance of acute lymphoblastic leukemia. Front Pediatr 2:53Google Scholar
  62. 62.
    Schlottmann I, Ehrhart-Bornstein M, Wabitsch M, Bornstein SR, Lamounier-Zepter V (2014) Calcium-dependent release of adipocyte fatty acid binding protein from human adipocytes. Int J Obes (Lond) 38(9):1221–1227Google Scholar
  63. 63.
    Cao H, Sekiya M, Ertunc ME, Burak MF, Mayers JR, White A et al (2013) Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production. Cell Metab 17(5):768–778Google Scholar
  64. 64.
    Hotamisligil GS, Bernlohr DA (2015) Metabolic functions of FABPs–mechanisms and therapeutic implications. Nat Rev Endocrinol 11(10):592–605Google Scholar
  65. 65.
    Maher M, Diesch J, Casquero R, Buschbeck M (2018) Epigenetic-transcriptional regulation of fatty acid metabolism and its alterations in leukaemia. Front Genet 9:405Google Scholar
  66. 66.
    Yan F, Shen N, Pang JX, Zhang YW, Rao EY, Bode AM et al (2017) Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive AML by enhancing aberrant DNA methylation in AML cells. Leukemia 31(6):42–1434Google Scholar
  67. 67.
    Abdelwahab SA, Owada Y, Kitanaka N, Adida A, Sakagami H, Ono M et al (2007) Enhanced expression of adipocyte-type fatty acid binding protein in murine lymphocytes in response to dexamethasone treatment. Mol Cell Biochem 299(1–2):99–107Google Scholar
  68. 68.
    Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP (2015) Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet 11(2):e1004901Google Scholar
  69. 69.
    Thomas D, Majeti R (2016) Burning fat fuels leukemic stem cell heterogeneity. Cell Stem Cell 19(1):1–2Google Scholar
  70. 70.
    Khandekar MJ, Cohen P, Spiegelman BM (2011) Molecular mechanisms of cancer development in obesity. Nat Rev Cancer 11(12):886–895Google Scholar
  71. 71.
    Rozovski U, Hazan-Halevy I, Barzilai M, Keating MJ, Estrov Z (2016) Metabolism pathways in chronic lymphocytic leukemia. Leuk Lymphoma 57(4):758–765Google Scholar
  72. 72.
    Rozovski U, Grgurevic S, Bueso-Ramos C, Harris DM, Li P, Liu Z et al (2015) Aberrant LPL expression, driven by STAT3, mediates free fatty acid metabolism in CLL cells. Mol Cancer Res 13(5):944–953Google Scholar
  73. 73.
    Ruby MA, Goldenson B, Orasanu G, Johnston TP, Plutzky J, Krauss RM (2010) VLDL hydrolysis by LPL activates PPAR-alpha through generation of unbound fatty acids. J Lipid Res 51(8):2275–2281Google Scholar
  74. 74.
    Tung S, Shi Y, Wong K, Zhu F, Gorczynski R, Laister RC et al (2013) PPARalpha and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia. Blood 122(6):969–980Google Scholar
  75. 75.
    Sheng X, Parmentier JH, Tucci J, Pei H, Cortez-Toledo O, Dieli-Conwright CM et al (2017) Adipocytes sequester and metabolize the chemotherapeutic daunorubicin. Mol Cancer Res 15(12):1704–1713Google Scholar
  76. 76.
    Cahu X, Calvo J, Poglio S, Prade N, Colsch B, Arcangeli M-L et al (2017) Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia. Blood Adv 1(20):1760–1772Google Scholar
  77. 77.
    Behan JW, Yun JP, Proektor MP, Ehsanipour EA, Arutyunyan A, Moses AS et al (2009) Adipocytes impair leukemia treatment in mice. Cancer Res 69(19):7867–7874Google Scholar
  78. 78.
    Pramanik R, Sheng X, Ichihara B, Heisterkamp N, Mittelman SD (2013) Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy. Leuk Res 37(5):503–509Google Scholar
  79. 79.
    Carneiro IP, Mazurak VC, Prado CM (2016) Clinical implications of sarcopenic obesity in cancer. Curr Oncol Rep 18(10):62Google Scholar
  80. 80.
    Bolan PJ, Arentsen L, Sueblinvong T, Zhang Y, Moeller S, Carter JS et al (2013) Water-fat MRI for assessing changes in bone marrow composition due to radiation and chemotherapy in gynecologic cancer patients. J Magn Reson Imaging 38(6):1578–1584Google Scholar
  81. 81.
    Liu H, Zhai Y, Zhao W, Wan Y, Lu W, Yang S et al (2018) Consolidation chemotherapy prevents relapse by indirectly regulating bone marrow adipogenesis in patients with acute myeloid leukemia. Cell Physiol Biochem 45(6):2389–2400Google Scholar
  82. 82.
    Dombret H, Gardin C (2016) An update of current treatments for adult acute myeloid leukemia. Blood 127(1):53–61Google Scholar
  83. 83.
    Miyashita T, Reed JC (1993) Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81(1):151–157Google Scholar
  84. 84.
    Zhang Y, Wang Z, Li X, Magnuson N (2008) Pim kinase-dependent inhibition of c-Myc degradation. Oncogene 27(35):4809Google Scholar
  85. 85.
    Sheng X, Tucci J, Parmentier JH, Ji L, Behan JW, Heisterkamp N et al (2016) Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response. Oncotarget 7(45):73147–73159Google Scholar
  86. 86.
    Fitter S, Dewar AL, Kostakis P, To LB, Hughes TP, Roberts MM et al (2008) Long-term imatinib therapy promotes bone formation in CML patients. Blood 111(5):2538–2547Google Scholar
  87. 87.
    Spaner DE (2012) Oral high-dose glucocorticoids and ofatumumab in fludarabine-resistant chronic lymphocytic leukemia. Leukemia 26(5):1144–1145Google Scholar
  88. 88.
    Wallace AM, Tucker P, Williams DM, Hughes IA, Ahmed SF (2003) Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia. Clin Endocrinol (Oxf) 58(6):770–776Google Scholar
  89. 89.
    Avramis VI, Tiwari PN (2006) Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int J Nanomed 1(3):241–254Google Scholar
  90. 90.
    Ehsanipour EA, Sheng X, Behan JW, Wang X, Butturini A, Avramis VI et al (2013) Adipocytes cause leukemia cell resistance to L-asparaginase via release of glutamine. Cancer Res 30–2998(10):7398Google Scholar
  91. 91.
    Mittelman SD, Orgel E (2018) Adipocyte metabolism of the chemotherapy daunorubicin. Oncoscience 5(5–6):146Google Scholar
  92. 92.
    Ye H, Adane B, Khan N, Ashton JM, Balys M, Stevens BM et al (2015) Adipose tissue functions as a reservoir for leukemia stem cells and confers chemo-resistance. Am Soc Hematol 6:845Google Scholar
  93. 93.
    Spindler TJ, Tseng AW, Zhou X, Adams GB (2013) Adipocytic cells augment the support of primitive hematopoietic cells in vitro but have no effect in the bone marrow niche under homeostatic conditions. Stem Cells Dev 23(4):434–441Google Scholar
  94. 94.
    Corre J, Planat-Benard V, Corberand JX, Pénicaud L, Casteilla L, Laharrague P (2004) Human bone marrow adipocytes support complete myeloid and lymphoid differentiation from human CD34+ cells. Br J Haematol 127(3):344–347Google Scholar
  95. 95.
    Glettig DL, Kaplan DL (2013) Extending human hematopoietic stem cell survival in vitro with adipocytes. Biores Open Access 2(3):179–185Google Scholar
  96. 96.
    Shafat MS, Gnaneswaran B, Bowles KM, Rushworth SA (2017) The bone marrow microenvironment–home of the leukemic blasts. Blood Rev 31(5):277–286Google Scholar
  97. 97.
    van Zoelen EJ, Duarte I, Hendriks JM, van der Woning SP (2016) TGFβ-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation. Stem Cell Res Ther 7(1):123Google Scholar

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Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Child Growth and Development Research CenterIsfahan University of Medical SciencesIsfahanIran
  3. 3.Department of Biochemistry and Hematology, Faculty of MedicineSemnan University of Medical SciencesSemnanIran
  4. 4.Thalassemia and Hemoglobinopathy Research Center, Research Institute of HealthAhvaz Jundishapur University of Medical SciencesAhvazIran

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