Transforming growth factor β- and interleukin 13-producing mast cells are associated with fibrosis in bone marrow.
Although bone marrow fibrosis is a lethal condition, its underlying mechanism is not fully understood. This study aimed to investigate the pathogenesis of fibrosis in the bone marrow through histologic examination of mast cell infiltration and the expression of fibrosis-associated cytokines. We analyzed 22 bone marrows with fibrosis (8 primary myelofibrosis [PMF], 5 post-essential thrombocythemia [ET], myelofibrosis, and 9 myelodysplastic syndrome [MDS] with bone marrow fibrosis [BMF]). Immunohistochemical and immunofluorescence stainings were performed using anti-mast cell tryptase, interleukin (IL) 13, transforming growth factor β (TGF-β), CD34, and CD42b antibodies. The number of mast cells in bone marrows with fibrosis was significantly higher than that in controls (P<.0001 for all cases with fibrosis versus control, P=.0470 for PMF versus control, P<.0001 post-ET myelofibrosis versus control, and P=.0005 for MDS with BMF versus control). Moreover, bone marrows with higher fibrotic grades exhibited greater amounts of infiltrating mast cells. Mast cells were positive for TGF-β and IL-13 in bone marrows with fibrosis of all 3 groups. Megakaryocytes were negative for TGF-β in post-ET and MDS with BMF, but some megakaryocytes in PMF were weakly positive for TGF-β. Megakaryocytes were negative for IL-13 in all 3 groups. Blasts were negative for both TGF-β and IL-13 in all 3 groups. Thus, TGF-β- and IL-13-producing mast cells might be key players in the development of BMF. Therefore, mast cells could be potential therapeutic targets for the treatment of BMF.
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan. Electronic address: in1304@osaka-med.ac.jp.
Shoko
S
Nakayama
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Taiji
T
Yokote
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Nobuya
N
Hiraoka
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Toshikazu
T
Akioka
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Uta
U
Nishiwaki
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Takuji
T
Miyoshi
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Kazuki
K
Iwaki
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Ayami
A
Fumimoto
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Yuki
Y
Masuda
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Jun
J
Hatooka
Department of Internal Medicine (I), Osaka Medical College, Osaka 569-0801, Japan.
Mayumi
M
Fujimoto
Division of Mathematics, Osaka Medical College, Osaka 569-0801, Japan.
Yasuichiro
Y
Nishimura
Division of Surgical Pathology, Osaka Medical College, Osaka 569-0801, Japan.
Motomu
M
Tsuji
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D018793:Interleukin-13 / Q000032:analysis*; D008297:Male; D008407:Mast Cells / Q000737:chemistry* / Q000473:pathology; D008533:Megakaryocytes / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications; D055728:Primary Myelofibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D013920:Thrombocythemia, Essential / Q000150:complications; D016212:Transforming Growth Factor beta / Q000032:analysis*
D018793:Interleukin-13; D016212:Transforming Growth Factor beta
Cytokine; Interleukin (IL) 13; Mast cell; Myelofibrosis; Transforming growth factor (TGF) β