General AML

Small bone marrow adipocytes in AML

Adipocytes have been reported to support the proliferation and survival of some solid tumor cells, for instance in breast and prostate cancer. Similarly, in vitro studies have shown that Bone Marrow (BM) adipocytes can support the survival of leukemic cells in Acute Myeloid Leukemia (AML).1 However, there is a paucity of studies that has investigated how these adipocytes are regulated by leukemic cells to promote disease progression, hence the rationale for this study.

Wei Lu et al. from the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China, in a Letter to the Editor of Haematologica, reported results from their study which investigated the impact of adipocytes, focusing specifically on their changing size in the BM samples from patients with primary AML.2

To assess the morphological characteristics of BM adipocytes, Lu et al. retrospectively analyzed the sizes of marrow adipocytes in the BM sections of primary AML patients (median age = 55 years [n = 70]) and compared it to controls (median age = 52 years [n = 70]). Based on treatment response, AML patients were divided into patients in remission (n = 32) and patients refractory to treatment (n = 38)

Based on the frequency distribution of adipocytes diameter or area in BM, adipocytes were categorized into three groups including small adipocytes (diameter < 42.6 µm), large adipocytes (diameter > 56.8 µm) and medium adipocytes (intermediate diameter)

The key findings of the study were:
  • Compared to the controls, only the small adipocytes were significantly higher in AML BM patient samples; 25% ± 8.9% vs 43.9% ± 19.3% respectively, P = 0.008
  • Volume and number of small adipocytes in patients in remission and refractory patients; 2.4% & 9.8 /mm2 vs 7.0 & 31.6 /mm2 respectively, P < 0.001

As a result of these findings, Lu et al. further investigated the prognostic impact of small adipocytes on the survival of AML patients.  

  • Overall Survival in patients with small adipocytes with a:
    • Volume of > 2.3% and < 2.3%; 11.5 vs 44.1 months, P < 0.001
    • Number of > 17.0/mm2 and < 17.0/mm2; 5.9 vs 33.0 months, P < 0.001
  • Relapse free survival in patients in remission with a:
    • Volume of > 2.5% and < 2.5%; 13.8 vs 44.3 months, P < 0.001
    • Number of > 9.2/mm2 and < 9.2/mm2; 14.0 vs 44.1 months, P < 0.001

In summary, small adipocytes were increased in AML patients and they may be a risk factor for poor prognosis of AML patients. Additionally, co-culturing of AML cell lines with primary AML derived BM adipocytes in vitro revealed that leukemic cells can promote the generation of small adipocytes which in turn promotes leukemic cell proliferation.

Overall, the results of this study indicates that BM small adipocytes could be used as an adverse prognostic factor for patients with AML and also serve as a basis for the concept of disrupting AML-adipocyte interactions as an approach for targeted therapy for AML.

References
  1. Shafat M.S. et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood. 2017 Mar 9; 129(10): 1320–1332. DOI: 10.1182/blood-2016-08-734798.
  2. Lu W. et al. Small Bone Marrow Adipocytes Predict Poor Prognosis In Acute Myeloid Leukaemia. Haematologica. 2017 Oct 19. DOI: 10.3324/haematol.2017.173492.