Predictive values of plasma TNF<strong>α</strong> and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

doi:10.1007/s11684-021-0890-1

Front. Med.

2022, Vol. 16

Issue (6) : 909-918 https://doi.org/10.1007/s11684-021-0890-1

RESEARCH ARTICLE

Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia

Fangyi Dong¹, Li Chen¹, Chaoxian Zhao^1,², Xiaoyang Li¹, Yun Tan^1,², Huan Song^1,², Wen Jin^1,², Hongming Zhu¹, Yunxiang Zhang¹, Kai Xue¹, Junmin Li¹(

), Kankan Wang^1,²(

)

¹. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 20025, China
². CNRS-LIA Hematology and Cancer, Sino-French Research Center for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

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Abstract

In patients with acute promyelocytic leukemia (APL), intracranial hemorrhage (ICH), if not identified promptly, could be fatal. It is the leading cause of failure of induction and early death. Thus, biomarkers that could promptly predict severe complications are critical. Here, cytokine differences between patients with APL with and without ICH were investigated to develop predictive models for this complication. The initial cytokine profiling using plasma samples from 39 patients and 18 healthy donors found a series of cytokines that were remarkedly different between patients with APL and healthy controls. The APL patients were subsequently divided into high and low white blood cell count groups. Results showed that tumor necrosis factor α and interleukin 8 (IL-8) were vital in distinguishing patients with APL who did or did not develop ICH. In addition, verification in 81 patients with APL demonstrated that the two cytokines were positively correlated with the cumulative incidence of ICH. Finally, in-vitro and in-vivo experimental evidence were provided to show that IL-8 influenced the migration of APL-derived NB4 cells and impaired the blood–brain barrier in PML/RARα positive blast-transplanted FVB/NJ mice. These assessments may facilitate the early warning of ICH and reduce future mortality levels in APL.

Keywords acute promyelocytic leukemia intracranial hemorrhage cytokines biomarker

Corresponding Author(s): Junmin Li,Kankan Wang

Just Accepted Date: 15 March 2022 Online First Date: 08 September 2022 Issue Date: 16 January 2023

Cite this article:

Fangyi Dong,Li Chen,Chaoxian Zhao, et al. Predictive values of plasma TNFα and IL-8 for intracranial hemorrhage in patients with acute promyelocytic leukemia[J]. Front. Med., 2022, 16(6): 909-918.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-021-0890-1
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I6/909

Tab.1 Clinical characteristics of 39 treatment-naive patients with APL

Cytokines (pg/mL)	Healthy controls (n = 18)(median (range))	Patients with APL (n = 39)(median (range))	P value
Basic FGF	2.39 (1.07−3.95)	29.1 (1.97−253.93)	< 0.001
CTACK	5.11 (2.8−10.22)	585.11 (243.35−2877.1)	< 0.001
Eotaxin	33.72 (8.63−55.5)	56.6 (21.29−177.12)	< 0.001
G-CSF	52.01 (9.07−85.56)	275.56 (113.91−7611.97)	< 0.001
GROα	45.42 (33.18−60.06)	516.44 (189.03−10 079.31)	< 0.001
HGF	247.66 (174.53−393.93)	3761.7 (529.4−72 585.02)	< 0.001
IFNγ	33.56 (14−62)	57.71 (19.57−225.62)	0.02
IL-1α	0 (0−0)	53.28 (19.57−150.54)	< 0.001
IL-1β	0 (0−1.77)	3.15 (0.97−69.81)	< 0.001
IL-10	0 (0−0)	10.48 (0.67−485.56)	< 0.001
IL-12(p70)	23.02 (10.39−55.65)	3.63 (0.93−145.74)	< 0.001
IL-13	0 (0−0.18)	0.46 (0.18−26.73)	< 0.001
IL-15	7.66 (2.06−10.86)	45.26 (6.16−1039.94)	0.137
IL-16	316.26 (91.93−518.35)	209.42 (48.75−4309.43)	0.287
IL-17	18.18 (4.77−81.27)	9.41 (4.77−190.99)	0.661
IL-18	58.99 (35.62−83.1)	65.8 (19.3−869.38)	0.336
IL-1Rα	138.7 (1.15−284.8)	251.04 (32.94−2359.54)	0.002
IL-2	0 (0−0)	2.82 (0.59−68.16)	< 0.001
IL-2Rα	47.68 (5.47−68.13)	144.31 (55.29−410.42)	< 0.001
IL-3	113.59 (81.26−139.97)	0.46 (0.11−11.29)	< 0.001
IL-5	0 (0−0)	25.2 (1.82−268.49)	< 0.001
IL-6	2.39 (1.01−4)	8.89 (2.06−126.56)	< 0.001
IL-8	9.34 (7.37−10.9)	93.92 (20.75−2118.03)	< 0.001
IL-9	36.88 (11.17−49.23)	39.04 (13.71−1745.51)	0.064
IP-10	333.26 (308.08−360.86)	754.46 (259.77−1933.17)	< 0.001
LIF	0 (0−0)	8.07 (2.11−515.68)	< 0.001
M-CSF	0 (0−0)	45.82 (26.27−173.27)	< 0.001
MCP-1	18.6 (11.02−21.94)	300.49 (26.2−843.85)	< 0.001
MIF	107.05 (83−128.74)	4578.01 (522.25−2 281 950)	< 0.001
MIG	905.23 (803.15−996.64)	714.58 (233.36−2577.87)	0.002
MIP-1β	34.92 (26.48−41.85)	75.1 (23.4−470.42)	< 0.001
PDGF-BB	942.4 (704.7−1089.1)	142.23 (67.41−2251.54)	< 0.001
RANTES	3.13 (2.07−3.98)	795.17 (54.21−15 337.05)	< 0.001
SCF	86.87 (68.55−110.14)	104.17 (37.77−202.57)	0.02
SCGFβ	33.62 (25.29−40.01)	741 584.86 (332 390.63−880 067.1)	< 0.001
SDF-1α	55.96 (13.4−94.5)	683.19 (195.57−1476.55)	< 0.001
TNFα	0 (0−0)	38.83 (10.41−328.32)	< 0.001
TNFβ	0 (0−0)	4.34 (0.25−108.2)	< 0.001
TRAIL	108.36 (89.49−129.95)	61.6 (21.31−173.42)	< 0.001
VEGF	24.18 (16.25−30.84)	361.78 (198.72−1040.59)	< 0.001
β-NGF	1.89 (1.08−2.89)	1.8 (0.26−113.03)	0.959

Tab.2 Spectrum of cytokines, chemokines, and growth factors in plasma of patients with APL compared with healthy donors

Fig.1 Comparison of plasma profiling of cytokines, chemokines, and growth factors between patients with APL-ICH and APL-non-ICH. The plasma levels of pro-inflammatory factors IL-2Rα and IL-8, and the cytokine HGF increased in patietns with APL-ICH compared with those without ICH. The plasma levels of the angiogenesis-promoting chemokine SDF-1α and the apoptosis-promoting cytokine TRAIL were lower in patients with APL-ICH than in those with APL-non-ICHs.

Tab.3 Top five ranked cytokines determined by random forest analysis with four different measures

Fig.2 Prediction of ICH-related outcomes via cytokine-based model. (A) Patients with increased IL-8 levels in the high WBC group exerted a significantly higher incidence of ICH (P = 0.008). (B) Patients with increased TNFα levels in the low WBC group had a higher incidence of ICH (P < 0.001).

Fig.3 Promotion of migration of NB4 cells and leakage of the blood–brain barrier by IL-8. (A,B) NB4 cell migration to the lower chamber significantly increased along with the IL-8 concentration in the lower chamber compared with the control group (P < 0.001, N = 4), as indicated by error bars. (C) Evans blue staining revealed increased permeability of the blood–brain barrier in IL-8-treated PML/RARα positive blast-transplanted FVB/NJ mice (n = 3). *** P < 0.001, **** P < 0.0001.

1	la Serna J de, P Montesinos, E Vellenga, C Rayón, R Parody, A León, J Esteve, JM Bergua, G Milone, G Debén, C Rivas, M González, M Tormo, J Díaz-Mediavilla, JD González, S Negri, E Amutio, S Brunet, B Lowenberg, MA Sanz. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 2008; 111( 7): 3395– 3402 https://doi.org/10.1182/blood-2007-07-100669 pmid: 18195095
2	M Yanada, T Matsushita, N Asou, Y Kishimoto, M Tsuzuki, Y Maeda, K Horikawa, M Okada, S Ohtake, F Yagasaki, T Matsumoto, Y Kimura, K Shinagawa, M Iwanaga, Y Miyazaki, R Ohno, T Naoe. Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome. Eur J Haematol 2007; 78( 3): 213– 219 https://doi.org/10.1111/j.1600-0609.2006.00803.x pmid: 17241371
3	AP Jillella, VK Kota. The global problem of early deaths in acute promyelocytic leukemia: a strategy to decrease induction mortality in the most curable leukemia. Blood Rev 2018; 32( 2): 89– 95 https://doi.org/10.1016/j.blre.2017.09.001 pmid: 29033137
4	S Mantha, DA Goldman, SM Devlin, JW Lee, D Zannino, M Collins, D Douer, HJ Iland, MR Litzow, EM Stein, FR Appelbaum, RA Larson, R Stone, BL Powell, S Geyer, K Laumann, JM Rowe, H Erba, S Coutre, M Othus, JH Park, PH Wiernik, MS Tallman. Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood 2017; 129( 13): 1763– 1767 https://doi.org/10.1182/blood-2016-10-747170 pmid: 28082441
5	Mantha S, Tallman MS, Devlin SM, Soff GA. Predictive factors of fatal bleeding in acute promyelocytic leukemia. Thromb Res 2018; 164(Supp 1): S98–S102
6	B De Boer, S Sheveleva, K Apelt, E Vellenga, AB Mulder, GH Schuringa, J Jacob. The IL1–IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis. Haematologica 2021; 106( 12): 3067– 3078 https://doi.org/10.3324/haematol.2020.254987 pmid: 33121233
7	D Forte, M García-Fernández, A Sánchez-Aguilera, V Stavropoulou, C Fielding, D Martín-Pérez, JA López, ASH Costa, L Tronci, E Nikitopoulou, M Barber, P Gallipoli, L Marando, de Castillejo CL Fernández, A Tzankov, S Dietmann, M Cavo, L Catani, A Curti, J Vázquez, C Frezza, BJ Huntly, J Schwaller, S Méndez-Ferrer. Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy. Cell Metab 2020; 32( 5): 829– 843.e9 https://doi.org/10.1016/j.cmet.2020.09.001 pmid: 32966766
8	L Stuani, JE Sarry. Microenvironmental aspartate preserves leukemic cells from therapy-induced metabolic collapse. Cell Metab 2020; 32( 3): 321– 323 https://doi.org/10.1016/j.cmet.2020.08.008 pmid: 32877685
9	E Bulaeva, D Pellacani, N Nakamichi, CA Hammond, PA Beer, A Lorzadeh, M Moksa, A Carles, M Bilenky, S Lefort, J Shu, BT Wilhelm, AP Weng, M Hirst, CJ Eaves. MYC-induced human acute myeloid leukemia requires a continuing IL-3/GM-CSF costimulus. Blood 2020; 136( 24): 2764– 2773 https://doi.org/10.1182/blood.2020006374 pmid: 33301029
10	M Yamashita, E Passegué. TNF-α coordinates hematopoietic stem cell survival and myeloid regeneration. Cell Stem Cell 2019; 25( 3): 357– 372.e7 https://doi.org/10.1016/j.stem.2019.05.019 pmid: 31230859
11	A Sinclair, L Park, M Shah, M Drotar, S Calaminus, LE Hopcroft, R Kinstrie, AV Guitart, K Dunn, SA Abraham, O Sansom, AM Michie, L Machesky, KR Kranc, GJ Graham, F Pellicano, TL Holyoake. CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells. Blood 2016; 128( 3): 371– 383 https://doi.org/10.1182/blood-2015-08-661785 pmid: 27222476
12	F Chen, K Zhou, L Zhang, F Ma, D Chen, J Cui, X Feng, S Yang, Y Chi, Z Han, F Xue, L Rong, M Ge, L Wan, S Xu, W Du, S Lu, H Ren, Z Han. Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways. Stem Cells Dev 2013; 22( 13): 1955– 1967 https://doi.org/10.1089/scd.2012.0621 pmid: 23391335
13	R Ma, T Li, M Cao, Y Si, X Wu, L Zhao, Z Yao, Y Zhang, S Fang, R Deng, VA Novakovic, Y Bi, J Kou, B Yu, S Yang, J Wang, J Zhou, J Shi. Extracellular DNA traps released by acute promyelocytic leukemia cells through autophagy. Cell Death Dis 2016; 7( 6): e2283 https://doi.org/10.1038/cddis.2016.186 pmid: 27362801
14	V Palibrk, R Suganthan, K Scheffler, W Wang, M Bjørås, SO Bøe. PML regulates neuroprotective innate immunity and neuroblast commitment in a hypoxic-ischemic encephalopathy model. Cell Death Dis 2016; 7( 7): e2320 https://doi.org/10.1038/cddis.2016.223 pmid: 27468695
15	KA Breen, D Grimwade, BJ Hunt. The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia. Br J Haematol 2012; 156( 1): 24– 36 https://doi.org/10.1111/j.1365-2141.2011.08922.x pmid: 22050876
16	MA Sanz, Coco F Lo, G Martín, G Avvisati, C Rayón, T Barbui, J Díaz-Mediavilla, G Fioritoni, JD González, V Liso, J Esteve, F Ferrara, P Bolufer, C Bernasconi, M Gonzalez, F Rodeghiero, D Colomer, MC Petti, JM Ribera, F Mandelli. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 2000; 96( 4): 1247– 1253 pmid: 10942364
17	L Breiman. Random Forests. Mach Learn 2001; 45( 1): 5– 32 https://doi.org/10.1023/A:1010933404324
18	A Liaw, M Wiener. Classification and regression by randomForest. R News 2002; 2 : 18– 22
19	S Lehmann, A Ravn, L Carlsson, P Antunovic, S Deneberg, L Möllgård, AR Derolf, D Stockelberg, U Tidefelt, A Wahlin, L Wennström, M Höglund, G Juliusson. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia 2011; 25( 7): 1128– 1134 https://doi.org/10.1038/leu.2011.78 pmid: 21502956
20	C Gurnari, M Breccia, F Di Giuliano, E Scalzulli, M Divona, A Piciocchi, L Cicconi, E De Bellis, A Venditti, MI Del Principe, W Arcese, F Lo-Coco, F Garaci, MT Voso. Early intracranial haemorrhages in acute promyelocytic leukaemia: analysis of neuroradiological and clinico-biological parameters. Br J Haematol 2021; 193( 1): 129– 132 https://doi.org/10.1111/bjh.17018 pmid: 32808672
21	B Sanchez-Correa, JM Bergua, C Campos, I Gayoso, MJ Arcos, H Bañas, S Morgado, JG Casado, R Solana, R Tarazona. Cytokine profiles in acute myeloid leukemia patients at diagnosis: survival is inversely correlated with IL-6 and directly correlated with IL-10 levels. Cytokine 2013; 61( 3): 885– 891 https://doi.org/10.1016/j.cyto.2012.12.023 pmid: 23357299
22	A Carey, DK 5th Edwards, CA Eide, L Newell, E Traer, BC Medeiros, DA Pollyea, MW Deininger, RH Collins, JW Tyner, BJ Druker, GC Bagby, SK McWeeney, A Agarwal. Identification of interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid leukemia. Cell Rep 2017; 18( 13): 3204– 3218 https://doi.org/10.1016/j.celrep.2017.03.018 pmid: 28355571
23	KR Katsumura, IM Ong, AW DeVilbiss, R Sanalkumar, EH Bresnick. GATA factor-dependent positive-feedback circuit in acute myeloid leukemia cells. Cell Rep 2016; 16( 9): 2428– 2441 https://doi.org/10.1016/j.celrep.2016.07.058 pmid: 27545880
24	S Binder, M Luciano, J Horejs-Hoeck. The cytokine network in acute myeloid leukemia (AML): a focus on pro- and anti-inflammatory mediators. Cytokine Growth Factor Rev 2018; 43 : 8– 15 https://doi.org/10.1016/j.cytogfr.2018.08.004 pmid: 30181021
25	KH Bi, GS Jiang. Relationship between cytokines and leukocytosis in patients with APL induced by all-trans retinoic acid or arsenic trioxide. Cell Mol Immunol 2006; 3( 6): 421– 427 pmid: 17257495
26	A Choudhry, TG DeLoughery. Bleeding and thrombosis in acute promyelocytic leukemia. Am J Hematol 2012; 87( 6): 596– 603 https://doi.org/10.1002/ajh.23158 pmid: 22549696
27	K Jambrovics, IP Uray, Z Keresztessy, JW Keillor, L Fésüs, Z Balajthy. Transglutaminase 2 programs differentiating acute promyelocytic leukemia cells in all-trans retinoic acid treatment to inflammatory stage through NF-κB activation. Haematologica 2019; 104( 3): 505– 515 https://doi.org/10.3324/haematol.2018.192823 pmid: 30237268
28	D Hanahan, RA Weinberg. Hallmarks of cancer: the next generation. Cell 2011; 144( 5): 646– 674 https://doi.org/10.1016/j.cell.2011.02.013 pmid: 21376230
29	S Trabanelli, MF Chevalier, A Martinez-Usatorre, A Gomez-Cadena, B Salomé, M Lecciso, V Salvestrini, G Verdeil, J Racle, C Papayannidis, H Morita, I Pizzitola, C Grandclément, P Bohner, E Bruni, M Girotra, R Pallavi, P Falvo, EO Leibundgut, GM Baerlocher, C Carlo-Stella, D Taurino, A Santoro, O Spinelli, A Rambaldi, E Giarin, G Basso, C Tresoldi, F Ciceri, D Gfeller, CA Akdis, L Mazzarella, S Minucci, PG Pelicci, E Marcenaro, ANJ McKenzie, D Vanhecke, G Coukos, D Mavilio, A Curti, L Derré, C Jandus. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nat Commun 2017; 8( 1): 593 https://doi.org/10.1038/s41467-017-00678-2 pmid: 28928446
30	A Mantovani, P Allavena, A Sica, F Balkwill. Cancer-related inflammation. Nature 2008; 454( 7203): 436– 444 https://doi.org/10.1038/nature07205 pmid: 18650914
31	WH Tsai, HC Hsu, CC Lin, CK Ho, YR Kou. Role of interleukin-8 and growth-regulated oncogene-alpha in the chemotactic migration of all-trans retinoic acid-treated promyelocytic leukemic cells toward alveolar epithelial cells. Crit Care Med 2007; 35( 3): 879– 885 https://doi.org/10.1097/01.CCM.0000256844.38259.27 pmid: 17235257
32	WH Tsai, CH Shih, CC Lin, CK Ho, FC Hsu, HC Hsu. Monocyte chemotactic protein-1 in the migration of differentiated leukaemic cells toward alveolar epithelial cells. Eur Respir J 2008; 31( 5): 957– 962 https://doi.org/10.1183/09031936.00135707 pmid: 18216048
33	P Ataca Atilla, MK McKenna, H Tashiro, M Srinivasan, F Mo, N Watanabe, BW Simons, A McLean Stevens, MS Redell, HE Heslop, M Mamonkin, MK Brenner, E Atilla. Modulating TNFα activity allows transgenic IL15-Expressing CLL-1 CAR T cells to safely eliminate acute myeloid leukemia. J Immunother Cancer 2020; 8( 2): e001229 https://doi.org/10.1136/jitc-2020-001229 pmid: 32938629
34	TY Kang, F Bocci, MK Jolly, H Levine, JN Onuchic, A Levchenko. Pericytes enable effective angiogenesis in the presence of proinflammatory signals. Proc Natl Acad Sci USA 2019; 116( 47): 23551– 23561 https://doi.org/10.1073/pnas.1913373116 pmid: 31685607
35	LCD Smyth, J Rustenhoven, TI Park, P Schweder, D Jansson, PA Heppner, SJ O’Carroll, EW Mee, RLM Faull, M Curtis, M Dragunow. Unique and shared inflammatory profiles of human brain endothelia and pericytes. J Neuroinflammation 2018; 15( 1): 138 https://doi.org/10.1186/s12974-018-1167-8 pmid: 29751771
36	A Volk, J Li, J Xin, D You, J Zhang, X Liu, Y Xiao, P Breslin, Z Li, W Wei, R Schmidt, X Li, Z Zhang, PC Kuo, S Nand, J Zhang, J Chen, J Zhang. Co-inhibition of NF-κB and JNK is synergistic in TNF-expressing human AML. J Exp Med 2014; 211( 6): 1093– 1108 https://doi.org/10.1084/jem.20130990 pmid: 24842373
37	TH Lee, ST Hsieh, HY Chiang. Fibronectin inhibitor pUR4 attenuates tumor necrosis factor α-induced endothelial hyperpermeability by modulating β1 integrin activation. J Biomed Sci 2019; 26( 1): 37 https://doi.org/10.1186/s12929-019-0529-6 pmid: 31096970
38	KS Doran, GY Liu, V Nizet. Group B streptococcal beta-hemolysin/cytolysin activates neutrophil signaling pathways in brain endothelium and contributes to development of meningitis. J Clin Invest 2003; 112( 5): 736– 744 https://doi.org/10.1172/JCI200317335 pmid: 12952922
39	BD Semple, T Kossmann, MC Morganti-Kossmann. Role of chemokines in CNS health and pathology: a focus on the CCL2/CCR2 and CXCL8/CXCR2 networks. J Cereb Blood Flow Metab 2010; 30( 3): 459– 473 https://doi.org/10.1038/jcbfm.2009.240 pmid: 19904283
40	L Meng, Y Zhao, W Bu, X Li, X Liu, D Zhou, Y Chen, S Zheng, Q Lin, Q Liu, H Sun. Bone mesenchymal stem cells are recruited via CXCL8-CXCR2 and promote EMT through TGF-β signal pathways in oral squamous carcinoma. Cell Prolif 2020; 53( 8): e12859 https://doi.org/10.1111/cpr.12859 pmid: 32588946
41	H Jayatilaka, P Tyle, JJ Chen, M Kwak, J Ju, HJ Kim, JSH Lee, PH Wu, DM Gilkes, R Fan, D Wirtz. Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration. Nat Commun 2017; 8( 1): 15584 https://doi.org/10.1038/ncomms15584 pmid: 28548090
42	P Cai, Q Wu, Y Wang, X Yang, X Zhang, S Chen. An effective early death scoring system for predicting early death risk in de novo acute promyelocytic leukemia. Leuk Lymphoma 2020; 61( 8): 1989– 1995 https://doi.org/10.1080/10428194.2020.1742910 pmid: 32228267
43	B Jin, Y Zhang, W Hou, F Cao, M Lu, H Yang, X Tian, Y Wang, J Hou, J Fu, H Li, J Zhou. Comparative analysis of causes and predictors of early death in elderly and young patients with acute promyelocytic leukemia treated with arsenic trioxide. J Cancer Res Clin Oncol 2020; 146( 2): 485– 492 https://doi.org/10.1007/s00432-019-03076-x pmid: 31686248
44	O Abla, RC Ribeiro, AM Testi, P Montesinos, U Creutzig, L Sung, G Di Giuseppe, D Stephens, JH Feusner, BL Powell, H Hasle, GJL Kaspers, L Dalla-Pozza, A Lassaletta, MS Tallman, F Locatelli, D Reinhardt, F Lo-Coco, J Hitzler, MA Sanz. Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy. Ann Hematol 2017; 96( 9): 1449– 1456 https://doi.org/10.1007/s00277-017-3042-6 pmid: 28597167

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[9]	Shuye Zhang, Fusheng Wang, Zheng Zhang. Current advances in the elimination of hepatitis B in China by 2030[J]. Front. Med., 2017, 11(4): 490-501.
[10]	Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan. Annexin A2-S100A10 heterotetramer is upregulated by PML/RARα fusion protein and promotes plasminogen-dependent fibrinolysis and matrix invasion in acute promyelocytic leukemia[J]. Front. Med., 2017, 11(3): 410-422.
[11]	Changlin Cao, Jingxian Gu, Jingyao Zhang. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases[J]. Front. Med., 2017, 11(2): 169-177.
[12]	Lei Huang,Aman Xu. Detection of digestive malignancies and post-gastrectomy complications via gastrointestinal fluid examination[J]. Front. Med., 2017, 11(1): 20-31.
[13]	Xiaoling Wang,Yun Tan,Yizhen Li,Jingming Li,Wen Jin,Kankan Wang. Repression of CDKN2C caused by PML/RARα binding promotes the proliferation and differentiation block in acute promyelocytic leukemia[J]. Front. Med., 2016, 10(4): 420-429.
[14]	Yi Cao. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications[J]. Front. Med., 2015, 9(3): 261-274.
[15]	Feng Wang,Chen Chen,Daowen Wang. Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets[J]. Front. Med., 2014, 8(4): 404-418.

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