Effects of Phenylhydrazine-induced Chronic Hemolytic Anemia on Peripheral Blood and Bone Marrow Stem Cells

doi:10.3969/j.issn.1671-2587.2026.01.004

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2026, Vol. 28 ›› Issue (1): 22-28.DOI: 10.3969/j.issn.1671-2587.2026.01.004

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Effects of Phenylhydrazine-induced Chronic Hemolytic Anemia on Peripheral Blood and Bone Marrow Stem Cells

LI Xinlei, AN Ning, WANG Yafen, WU Xiaoshuang, CHEN Jie, HE Yang, CHEN Yaozhen, HU Xingbin

Northwest University; Department of Blood Transfusion, Xijing Hospital, Air Force Military Medical University; Department of Blood Transfusion, Qujiang New District Hospital, Xi'an 710000

Received:2025-05-15 Published:2026-02-13

Abstract

Abstract: Objective To investigate the effects of multi-level regulatory effects within the hematopoietic system in a murine model of phenylhydrazine(PHZ)-induced chronic hemolytic anemia. Methods A chronic hemolytic anemia model was established in C57BL/6 mice using PHZ. We analyzed multiple hematopoietic parameters, including complete blood count, plasma-free hemoglobin, and flow cytometric quantification of terminal erythroid differentiation stages, hematopoietic stem cells (HSCs) , and bone marrow mesenchymal stem cells (BMSCs). Results Successful model establishment was confirmed by complete blood count and elevated free hemoglobin. Flow cytometry revealed significant increases in the proportions of proerythroblasts [(2.33±0.29)%, P<0.01] and basophilic erythroblasts [(1.04±0.23)%, P<0.05]. Additionally, the proportions of HSCs [(0.16±0.03)%, P<0.000 1] and BMSCs were significantly elevated in the bone marrow. Conclusion PHZ-induced chronic hemolytic anemia triggers multi-level regulation within the hematopoietic system, which helps maintain erythrocyte homeostasis and provides a theoretical basis for understanding the pathogenesis of hemolytic anemia.

Key words: Phenylhydrazine, Chronic hemolytic anemia, Red blood cell, Bone marrow mesenchymal stem cell, Bone marrow hematopoietic system

CLC Number:

R556.6R329.2

LI Xinlei, AN Ning, WANG Yafen, WU Xiaoshuang, CHEN Jie, HE Yang, CHEN Yaozhen, HU Xingbin. Effects of Phenylhydrazine-induced Chronic Hemolytic Anemia on Peripheral Blood and Bone Marrow Stem Cells[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2026, 28(1): 22-28.

References

[1] KHURANA K,MAHAJAN S,ACHARYA S,et al.Clinical biomarkers of acute vaso-occlusive sickle cell crisis[J]. Cureus,2024,16(3):e56389.
[2] BARCELLINI W,FATTIZZO B.Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic Anemia[J]. Dis Markers,2015, 2015:635670.
[3] BERENTSEN S,VOS J M I,MALECKA A,et al. The impact of individual clinical features in cold agglutinin disease: hemolytic versus non-hemolytic symptoms[J]. Expert Rev Hematol,2024,17(8):479-492.
[4] QUINTANA-BUSTAMANTE O,FAÑANAS-BAQUERO S,DESSY-RODRIGUEZ M,et al. Gene editing for inherited red blood cell diseases[J]. Front Physiol,2022, 13:848261.
[5] MICHEL M.Classification and therapeutic approaches in autoimmune hemolytic Anemia: an update[J]. Expert Rev Hematol,2011,4(6):607-618.
[6] TOLE S,DHIR P,PUGI J,et al.Genotype-phenotype correlation in children with hereditary spherocytosis[J]. Br J Haematol,2020,191(3):486-496.
[7] SÁNCHEZ N,ZUBICARAY J,SEBASTIÁN E,et al. Autoimmune hemolytic Anemia: Case review[J]. An Pediatr,2021,94(4):206-212.
[8] WACHTER F,ARCHER N M.Autoimmune hemolytic Anemia complicated by parvovirus infection[J]. Blood, 2021,137(8):1130.
[9] HURTADO J,SELLAK H,JOSEPH G,et al.Accelerated atherosclerosis in beta-thalassemia[J]. Am J Physiol Heart Circ Physiol,2023,325(5):H1133-H1143.
[10] ANBARA H,SHAHROOZ R,RAZI M,et al.Repro-protective role of royal jelly in phenylhydrazine-induced hemolytic Anemia in male mice: Histopathological, embryological,and biochemical evidence[J]. Environ Toxicol,2022,37(5):1124-1135.
[11] MEMISOGLU A,KOLGAZI M,YAMAN A, et al.Neuroprotective effect of erythropoietin on phenylhydrazine-induced hemolytic hyperbilirubinemia in neonatal rats[J]. Neurochem Res,2017,42(4):1026-1037.
[12] JIA S H,ZHANG L B,LIU H L,et al.Upgrading of nitrate to hydrazine through cascading electrocatalytic ammonia production with controllable N-N coupling[J]. Nat Commun,2024,15(1):8567.
[13] JIA X E,MA K,XU T,et al.Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction[J]. Cell Res,2015,25(8): 946-962.
[14] LYU J H,GU Z M,ZHANG Y,et al. A glutamine metabolic switch supports erythropoiesis[J]. Science, 2024,386(6723):eadh9215.
[15] SUNDARAM B,PANDIAN N,MALL R,et al. NLRP12-PANoptosome activates PANoptosis and pathology in response to heme and PAMPs[J]. Cell,2023,186(13): 2783-2801.e20.
[16] 胡巍. 褪黑素对伽马射线辐射损伤密质骨间充质干细胞的缓解作用及应用研究[D]. 北京:中国人民解放军医学院,2022.
[17] HU X B,GARCIA M,WENG L H,et al.Identification of a common mesenchymal stromal progenitor for the adult haematopoietic niche[J]. Nat Commun,2016,7:13095.
[18] 陈要臻,胡兴斌,尹文,等. 骨相关间充质干细胞CD166+亚群的制备及应用:CN112159794 A[P].2021-01-01.
[19] D'ALESSANDRO A,HAY A,DZIECIATKOWSKA M,et al. Protein-L-isoaspartate O-methyltransferase is required for in vivo control of oxidative damage in red blood cells[J]. Haematologica,2021,106(10):2726-2739.
[20] CHIANG J C,CHEN W M,LIN K H,et al.Lysophosphatidic acid receptors 2 and 3 regulate erythropoiesis at different hematopoietic stages[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2021, 1866(1):158818.
[21] PEI S Y,WANG Y J,YAO R,et al.Whole blood exchange ameliorates acute hemolytic Anemia by reducing inflammation and oxidative stress in rats[J]. FASEB J, 2025,39(2):e70358.
[22] OKAFOR A I,ATSU C U.Ficus glumosa Del. reduces phenylhydrazine-induced hemolytic anaemia and hepatic damage in Wistar rats[J]. J Complement Integr Med, 2022,19(3):661-668.
[23] ROSTAMI T,MALEKI N,KASAEIAN A,et al.Co-transplantation of bone marrow-derived mesenchymal stem cells with hematopoietic stem cells does not improve transplantation outcome in class Ⅲ beta-thalassemia major: A prospective cohort study with long-term follow-up[J]. Pediatr Transplant,2021,25(3):e13905.
[24] NICKEL R S,QAYED M,WORTHINGTON-WHITE D,et al. Infusion hemolysis after pediatric major ABO-mismatched bone marrow transplant: Comparison of two red blood cell depletion techniques[J]. Pediatr Blood Cancer,2018,65(3):10.1002/pbc.26883.
[25] KACZANOWSKA S,BEURY D W,GOPALAN V,et al. Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis[J]. Cell, 2021,184(8):2033-2052.e21.
[26] MINCIACCHI V R,BRAVO J,KARANTANOU C,et al.Exploitation of the fibrinolytic system by B-cell acute lymphoblastic leukemia and its therapeutic targeting[J]. Nat Commun,2024,15(1):10059.
[27] TIKHONOVA A N,DOLGALEV I,HU H,et al.The bone marrow microenvironment at single-cell resolution[J]. Nature,2019,569(7755):222-228.
[28] FORTE D,GARCÍA-FERNÁNDEZ M,SÁNCHEZ-AGUILERA A,et al. Bone marrow mesenchymal stem cells support acute myeloid leukemia bioenergetics and enhance antioxidant defense and escape from chemotherapy[J]. Cell Metab,2020,32(5):829-843.e9.
[29] RAMLOGAN-STEEL C A,STEEL J C,FATHALLAH H,et al. Stathmin 1 deficiency induces erythro-megakaryocytic defects leading to macrocytic Anemia and thrombocythemia in Stathmin 1 knock out mice[J]. Blood Cells Mol Dis,2021,87:102522.
[30] KATSURAGI S,OHTO H,YOSHIDA A,et al.Anemic disease of the newborn with little increase in hemolysis and erythropoiesis due to maternal anti-jr(a): a case study and review of the literature[J]. Transfus Med Rev, 2019,33(3):183-188.
[31] PANDEY S,GANESHPURKAR A,BANSAL D,et al.Hematopoietic effect of Amaranthus cruentus extract on phenylhydrazine-induced toxicity in rats[J]. J Diet Suppl,2016,13(6):607-615.
[32] JU W,LU W Y,DING L,et al.PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation[J]. J Biomed Sci,2020,27(1):91.

Effects of Phenylhydrazine-induced Chronic Hemolytic Anemia on Peripheral Blood and Bone Marrow Stem Cells

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