Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted.
Vitamin B6 deficiency Myelofibrosis Cancer Oncogenesis Anemia
This is a preview of subscription content, log in to check access.
We thank Kyoko Kubo, Keiko Terao, Kazuko Kawamura, and Megumi Hasegawa for their superb secretarial assistance.
Compliance with ethical standard
Conflict of interest
The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript.
Galluzzi L, Vacchelli E, Michels J, Garcia P, Kepp O, Senovilla L, et al. Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses. Oncogene. 2013;32:4995–5004.CrossRefGoogle Scholar
Rojer RA, Mulder NH, Nieweg HO. Response to pyridoxine hydrochloride in refractory anemia due to myelofibrosis. Am J Med. 1978;65:655–60.CrossRefGoogle Scholar
Shirane S, Araki M, Morishita S, Edahiro Y, Sunami Y, Hironaka Y, et al. Consequences of the JAK2V617F allele burden for the prediction of transformation into myelofibrosis from polycythemia vera and essential thrombocythemia. Int J Hematol. 2015;101:148–53.CrossRefGoogle Scholar
Combs GF. The vitamins: fundamental aspects in nutrition and health. Newyork: Academic Press; 2012. p. 309–23.CrossRefGoogle Scholar
Misawa K, Yasuda H, Araki M, Ochiai T, Morishita S, Shirane S, et al. Mutational subtypes of JAK2 and CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms. Int J Hematol. 2018;107:673–80.CrossRefGoogle Scholar
Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRefGoogle Scholar
Yasuda H, Fujiwara N, Ishizaki Y, Komatsu N. Anemia attributed to vitamin B6 deficiency in post-pancreaticoduodenectomy patients. Pancreatology. 2015;15:81–3.CrossRefGoogle Scholar
Suzuki M, Nakagawa M, Shimizu Y, Suemura M, Sato B. Therapy-resistant microcytic hypochromic anemia from malabsorption-related vitamin B6 deficiency after a gastrointestinal operation. Rinsho Ketsueki. 2005;46:1044–8.Google Scholar
Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5′-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr. 2008;87:1446–54.CrossRefGoogle Scholar
Aranda F, Bloy N, Pesquet J, Petit B, Chaba K, Sauvat A, et al. Immune-dependent antineoplastic effects of cisplatin plus pyridoxine in non-small-cell lung cancer. Oncogene. 2015;34:3053–62.CrossRefGoogle Scholar
Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17:97–111.CrossRefGoogle Scholar
Ha C, Miller LT, Kerkvliet NI. The effect of vitamin B6 deficiency on cytotoxic immune responses of T cells, antibodies, and natural killer cells, and phagocytosis by macrophages. Cell Immunol. 1984;85:318–29.CrossRefGoogle Scholar
Qian B, Shen S, Zhang J, Jing P. Effects of vitamin B6 deficiency on the composition and functional potential of T cell populations. J Immunol Res. 2017;2017:2197975.CrossRefPubMedCentralGoogle Scholar
Marzio A, Merigliano C, Gatti M, Vernì F. Sugar and chromosome stability: clastogenic effects of sugars in vitamin B6-deficient cells. PLoS Genet. 2014;10:e1004199.CrossRefPubMedCentralGoogle Scholar
Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol. 2007;139:351–62.CrossRefGoogle Scholar
Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. 2006;29:317–26.CrossRefGoogle Scholar