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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Acute Myeloid Leukemia | Research

Influence on therapeutic outcome of platelet count at diagnosis in patients with de novo non-APL acute myeloid leukemia

Authors: Yujiao Zhang, Quan Wu, Baoyi Yuan, Yun Huang, Ling Jiang, Fang Liu, Ping Yan, Yongshuai Jiang, Jieyu Ye, Xuejie Jiang

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Platelet (PLT) count at diagnosis plays an important role in cancer development and progression in solid tumors. However, it remains controversial whether PLT count at diagnosis influences therapeutic outcome in patients with non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML).

Methods

This study analyzed the relationship between PLT count at diagnosis and genetic mutations in a cohort of 330 newly diagnosed non-APL AML patients. The impact of PLT count on complete remission, minimal residual disease status and relapse-free survival (RFS) were evaluated after chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Results

Our studies showed that patients with DNMT3A mutations have a higher PLT count at diagnosis, while patients with CEBPA biallelic mutations or t(8;21)(q22; q22) translocation had lower PLT count at diagnosis. Furthermore, non-APL AML patients with high platelet count (> 65 × 109/L) at diagnosis had worse response to induction chemotherapy and RFS than those with low PLT count. In addition, allo-HSCT could not absolutely attenuated the negative impact of high PLT count on the survival of non-APL AML patients.

Conclusion

PLT count at diagnosis has a predictive value for therapeutic outcome for non-APL AML patients.
Appendix
Available only for authorised users
Literature
1.
Papaemmanuil E, et al. Genomic classification and prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374(23):2209–21.PubMedPubMedCentral
2.
Döhner H, Wei AH. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN 2022. 140(12): p. 1345–1377.
3.
Tefferi A, Letendre L. Going beyond 7 + 3 regimens in the treatment of adult acute Myeloid Leukemia. J Clin Oncol. 2012;30(20):2425–8.PubMed
4.
Short NJ, Rytting ME, Cortes JE. Acute Myeloid Leukaemia Lancet. 2018;392(10147):593–606.PubMed
5.
Chen X, et al. Relation of clinical response and minimal residual Disease and their prognostic impact on outcome in acute Myeloid Leukemia. J Clin Oncol. 2015;33(11):1258–64.PubMed
6.
Paiva B, Vidriales MB. Impact of measurable residual Disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute Myeloid Leukemia. 2021. 35(8): p. 2358–70.
7.
Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016;127(1):62–70.PubMed
8.
Schmid C, et al. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. Blood. 2015;126(17):2062–9.PubMed
9.
Döhner H, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47.PubMedPubMedCentral
10.
Greenwood MJ, et al. Leukocyte count as a predictor of death during remission induction in acute Myeloid Leukemia. Leuk Lymphoma. 2006;47(7):1245–52.PubMed
11.
Kelaidi C, Adès L, Fenaux P. Treatment of acute promyelocytic Leukemia with high white cell blood counts. Mediterr J Hematol Infect Dis. 2011;3(1):e2011038.PubMedPubMedCentral
12.
Qian X, Wen-jun L. Platelet changes in acute Leukemia. Cell Biochem Biophys. 2013;67(3):1473–9.PubMed
13.
Hu X, et al. Kinetics of normal hematopoietic stem and progenitor cells in a Notch1-induced Leukemia model. Blood. 2009;114(18):3783–92.PubMedPubMedCentral
14.
15.
Radziwon-Balicka A, et al. Platelets increase survival of adenocarcinoma cells challenged with anticancer Drugs: mechanisms and implications for chemoresistance. Br J Pharmacol. 2012;167(4):787–804.PubMedPubMedCentral
16.
Mammadova-Bach E, et al. Platelet glycoprotein VI promotes Metastasis through interaction with cancer cell-derived galectin-3. Blood. 2020;135(14):1146–60.PubMed
17.
Thies KA, Hammer AM, Hildreth BE 3. Stromal Platelet-Derived Growth Factor Receptor-β Signaling Promotes Breast Cancer Metastasis in the Brain. 2021;81(3):606–18.
18.
Chen YP, et al. Pretreatment platelet count improves the prognostic performance of the TNM staging system and Aids in planning therapeutic regimens for nasopharyngeal carcinoma: a single-institutional study of 2,626 patients. Chin J Cancer. 2015;34(3):137–46.PubMed
19.
Ikeda M, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 2002;9(3):287–91.PubMed
20.
Yuan Y, et al. Prognostic value of pretreatment platelet counts in Lung cancer: a systematic review and meta-analysis. BMC Pulm Med. 2020;20(1):96.PubMedPubMedCentral
21.
Bensalah K, et al. Prognostic value of thrombocytosis in renal cell carcinoma. J Urol. 2006;175(3 Pt 1):859–63.PubMed
22.
Cacic D, Reikvam H. Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis 2021. 13(8).
23.
Cacic D et al. Platelet microparticles decrease Daunorubicin-Induced DNA damage and modulate intrinsic apoptosis in THP-1 cells. Int J Mol Sci, 2021. 22(14).
24.
Zhang Q, et al. Pretreatment platelet count predicts survival outcome of patients with de novo non-M3 acute Myeloid Leukemia. PeerJ. 2017;5:e4139.PubMedPubMedCentral
25.
Zhang Y, et al. Low platelet counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia. Acta Haematol. 2020;143(1):9–18.PubMed
26.
Swerdlow SH et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms 2016. 127(20): p. 2375-90.
27.
Xuan L, et al. Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus Infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies. J Hematol Oncol. 2012;5:46.PubMedPubMedCentral
28.
Cheson BD, et al. Revised recommendations of the International Working Group for Diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in Acute Myeloid Leukemia. J Clin Oncol. 2003;21(24):4642–9.PubMed
29.
Cai SF, Levine RL. Genetic and epigenetic determinants of AML pathogenesis. Semin Hematol. 2019;56(2):84–9.PubMed
30.
Patel JP, et al. Prognostic relevance of integrated genetic profiling in acute Myeloid Leukemia. N Engl J Med. 2012;366(12):1079–89.PubMedPubMedCentral
31.
Ley TJ, et al. DNA sequencing of a cytogenetically normal acute myeloid Leukaemia genome. Nature. 2008;456(7218):66–72.PubMedPubMedCentral
32.
Trafalis DT, et al. Platelet production and related pathophysiology in acute myelogenous Leukemia at first diagnosis: prognostic implications. Oncol Rep. 2008;19(4):1021–6.PubMed
33.
Kuo KH, et al. A retrospective observational study of leucoreductive strategies to manage patients with acute myeloid Leukaemia presenting with hyperleucocytosis. Br J Haematol. 2015;168(3):384–94.PubMed
34.
Wahlin A, et al. Results of risk-adapted therapy in acute myeloid Leukaemia. A long-term population-based follow-up study. Eur J Haematol. 2009;83(2):99–107.PubMed
35.
Canaani J, et al. Long term impact of hyperleukocytosis in newly diagnosed acute Myeloid Leukemia patients undergoing allogeneic stem cell transplantation: an analysis from the acute Leukemia working party of the EBMT. Am J Hematol. 2017;92(7):653–9.PubMed
36.
Malagola M, et al. A simple prognostic scoring system for newly diagnosed cytogenetically normal acute Myeloid Leukemia: retrospective analysis of 530 patients. Leuk Lymphoma. 2011;52(12):2329–35.PubMed
37.
Schlenk RF, et al. Mutations and treatment outcome in cytogenetically normal acute Myeloid Leukemia. N Engl J Med. 2008;358(18):1909–18.PubMed
38.
Shi L, et al. Predictable resistance and overall survival of Gemcitabine/Cisplatin by platelet activation index in Non-small Cell Lung Cancer. Med Sci Monit. 2018;24:8655–68.PubMedPubMedCentral
39.
Casagrande N, Borghese C, Agostini F. In Ovarian Cancer Multicellular Spheroids, Platelet Releasate Promotes Growth, Expansion of ALDH + and CD133 + Cancer Stem Cells, and Protection against the Cytotoxic Effects of Cisplatin, Carboplatin and Paclitaxel 2021. 22(6).
40.
41.
Wang YH, et al. The pretreatment thrombocytosis may predict prognosis of patients with Colorectal cancer: a systematic review and meta-analysis. Biomark Med. 2017;11(2):195–210.PubMed
42.
Foss B, Bruserud O. Platelet functions and clinical effects in acute myelogenous Leukemia. Thromb Haemost. 2008;99(1):27–37.PubMed
43.
Paek SC, Min SK, Park JB. Effects of platelet-derived growth factor-BB on cellular morphology and cellular viability of stem cell spheroids composed of bone-marrow-derived stem cells. Biomed Rep. 2020;13(6):59.PubMedPubMedCentral
44.
Etxabe A, et al. Inhibition of serotonin receptor type 1 in acute Myeloid Leukemia impairs Leukemia stem cell functionality: a promising novel therapeutic target. Leukemia. 2017;31(11):2288–302.PubMed
45.
Nara N, et al. Inhibition of the in vitro growth of blast progenitors from acute myeloblastic Leukemia patients by transforming growth factor-beta (TGF-beta). Leukemia. 1989;3(8):572–7.PubMed
46.
Binder S, Luciano M, Horejs-Hoeck J. The cytokine network in acute Myeloid Leukemia (AML): a focus on pro- and anti-inflammatory mediators. Cytokine Growth Factor Rev. 2018;43:8–15.
47.
Huang WK, et al. miR-125a-5p regulation increases phosphorylation of FAK that contributes to imatinib resistance in gastrointestinal stromal tumors. Exp Cell Res. 2018;371(1):287–96.PubMed
48.
Hirao A, Sato Y. MiR-125b-5p Is Involved in Sorafenib Resistance through Ataxin-1-Mediated Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma 2021. 13(19).
49.
Bai H, et al. Involvement of miR-125a in resistance to daunorubicin by inhibiting apoptosis in Leukemia cell lines. Tumour Biol. 2017;39(4):1010428317695964.PubMed
50.
Zhang L, et al. Platelet-acute Leukemia interactions. Clin Chim Acta. 2022;536:29–38.PubMed
51.
Chou FS, Mulloy JC. The thrombopoietin/MPL pathway in hematopoiesis and leukemogenesis. J Cell Biochem. 2011;112(6):1491–8.PubMed
52.
Solar GP, et al. Role of c-mpl in early hematopoiesis. Blood. 1998;92(1):4–10.PubMed
53.
Dong-Feng Z, et al. The TPO/c-MPL pathway in the bone marrow may protect Leukemia cells from chemotherapy in AML patients. Pathol Oncol Res. 2014;20(2):309–17.PubMed
54.
Yoshihara H, et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007;1(6):685–97.PubMed
55.
Thol F, et al. Incidence and prognostic influence of DNMT3A mutations in acute Myeloid Leukemia. J Clin Oncol. 2011;29(21):2889–96.PubMed
56.
Xing S et al. Cytogenetics and associated mutation profile in patients with acute monocytic Leukemia. 2019. 41(4): p. 485–92.
57.
Yang L, et al. DNMT3A R882 mutation is associated with elevated expression of MAFB and M4/M5 immunophenotype of acute Myeloid Leukemia blasts. Leuk Lymphoma. 2015;56(10):2914–22.PubMed
58.
Rauch PJ, et al. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. Blood. 2016;128(18):2253–7.PubMed
59.
Grigg AP, et al. Clinical, haematological and cytogenetic features in 24 patients with structural rearrangements of the Q arm of chromosome 3. Br J Haematol. 1993;83(1):158–65.PubMed
60.
Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies 2017. 129(15): p. 2070–2082.
Metadata
Title
Influence on therapeutic outcome of platelet count at diagnosis in patients with de novo non-APL acute myeloid leukemia
Authors
Yujiao Zhang
Quan Wu
Baoyi Yuan
Yun Huang
Ling Jiang
Fang Liu
Ping Yan
Yongshuai Jiang
Jieyu Ye
Xuejie Jiang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11543-5

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