Letters to the Editor / Leukemia Research 31 (2007) 1449–1455 1453 of GATA1 mutations [6]. At the same time, it has been shown that hyperdiploid lymphoblasts in some of these patients generate significantly higher levels of the active intracellular form of methotrexate, polyglutamates [7,8]. The possible explanation is the reduced folate carrier gene localized to short arm of chromosome 21 which is expressed at significantly higher levels in hyperdiploid lymphoblasts compared to non-hyperdiploid lymphoblasts [9]. This gene encodes the protein, which transports intracellularly reduced folates including methotrexate and accounts for the greater generation of the polyglutamates and ensuing toxicity [9]. This report should instigate a change in the UK ALL XII protocol to suggest the importance of identifying the diploidy pattern in individuals with trisomy 21 who need treatment for ALL. In such individuals, if a hyperdiploid pattern is observed, there is a need to consider reduction of the dose of Methotrexate administered during the consolidation phase to limit toxicity. Acknowledgements The author is responsible for the collection of the clinical data and drafting of the paper and describes no conflicts of interest in publication of this paper. References [1] Pauley JL, Panetta JC, Schmidt J, Kornegay N, Relling MV, Pui CH. Late- onset delayed excretion of methotrexate. Cancer Chemother Pharmacol 2004;54:146–52. [2] Ravindranath Y, Abella E, Krischer J, et al. Acute myeloid leukemia (AML) in Down’s syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML study 8498. Blood 1992;80:2210–4. [3] Lie SO, Jonmundsson G, Mellander I, et al. A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and chil- dren with Down’s syndrome. Nordic Society of Paediatric Haematology and Oncology (NOPHO). Br J Haematol 1996;94:82–8. [4] Taub JW, Matherly LH, Stout ML, et al. Enhanced metabolism of 1-ß-D-arabinofuranosyl-cytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syn- drome children with acute myeloid leukemia. Blood 1996;87:3395– 403. [5] Taub JW, Huang X, Matherly LH, et al. Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down Syndrome and non-Down Syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Blood 1999;94:1393–400. [6] Zwaan CM, Kaspers GJ, Pieters R, et al. Different drug sensitivity pro- files of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood 2002;99:245–51. [7] Whitehead VM, Vuchich MJ, Lauer SJ, et al. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (>50 chromosomes) B-lineage acute lym- phoblastic leukaemia. A Pediatric Oncology Group study. Blood 1992;80:1316–623. [8] Synold TW, Relling MV, Boyett JM, et al. Blast cell methotrex- ate polyglutamate accumulation in vivo differs by lineage, ploidy, and methotrexate dose in acute lymphoblastic leukemia. J Clin Invest 1994;94:1996–2001. [9] BelkovVM, Krynetski EY, Schuetz JD, et al. Reduced folate car- rier expression in acute lymphoblastic leukemia: a mechanism for ploidy but not lineage differences in methotrexate accumulation. Blood 1999;93:1643–50. Jecko Thachil ∗ Royal Liverpool University Hospital, Haematology, Prescot St, Liverpool L7 8XP, United Kingdom ∗ Tel.: +44 1514310079. E-mail address: jeckothachil@yahoo.co.uk 6 November 2006 Available online 18 December 2006 doi: 10.1016/j.leukres.2006.11.005 PEG-Filgrastim activity on granulocyte functions Recombinant human G-CSF Filgrastim is used after chemotherapy to reduce the risk of severe neutropenia-related infections, while high doses are successfully employed to mobilize stem cells with transplant finalities. However, several modifications in granulocytes (PMN) morphology and function have been reported due to Fil- grastim treatment, as polarization or presence of membrane blebs. These morphological abnormalities correlate with a deficit of PMN chemotaxis [1], and may be related to the cytoskeleton rearrangement related to F-actin polymerization [2,3]. In vivo Filgrastim-pulsed PMN F-actin polymerization, membrane-linked RhoA, and cell polarization are enhanced; the basal hyper activation of RhoA may be responsible for morphological and functional modifications of Filgrastim- mobilized cells. These Filgrastim pulsed cells are unable to correctly respond to LPS stimulation. Additionally, Filgras- tim is able to correct in vitro the defective polarization of chemoattractant-induced cytoskeletal rearrangement of PMN in patients with severe infections of the airways [5]. All the above reported data that Filgrastim induces cytoskeletal rear- rangements and thus it is able to induce a PMN functional “paralysis”, related to a hyper activation. Interestingly, Lenograstim, a glycosylated recombinant human G-CSF, does not induce such morphological and functional modifications [1,4,6]. Moreover, in vivo Lenograstim-pulsed PMNs show a normal RhoA activation and cellular elongation capability when exposed to LPS [4]. A possible explanation of the divergent effects of these very similar agents could be related to the more stable serum levels of Lenograstim when compared to Filgrastim. Con- sidering the long lasting half-life and the serum stability of the polyethylene glycol (PEG)-conjugated Filgrastim (Peg- filgrastim) we evaluated if the action of this drug will differ from the native Filgrastim formulation.