Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report four patients with MDS with erythroid hypoplasia who received immunosuppressive therapy. All were elderly, had severe transfusion‐dependent anaemia, morphological evidence of myelodysplasia and a low percentage (3·2–13·6%) of erythroid precursors. Administration of cyclosporin A (CsA) improved their anaemia; all transfusion‐dependent patients achieved transfusion‐independence. An inverted CD4/8 ratio was seen in three patients who also demonstrated T‐cell receptor (TCR)‐β and ‐γ gene rearrangements by Southern blotting and clonality by polymerase chain reaction. Treatment with CsA can be an attractive alternative treatment for patients with MDS with erythroid hypoplasia, which may be associated with a clonal abnormality in T cells.
We have previously reported that vitamin K 2 (VK2) has a potent apoptosis inducing activity toward various types of primary cultured leukemia cells including acute myelogenous leukemia arising from myelodysplastic syndromes (MDS). We estab-
Summary. We encountered a patient with Philadelphianegative chronic myeloid leukaemia, with t(7;11)(p15;p15), in whom acute leukaemia phase (acute myeloid leukaemia-M2 morphology) developed within a short period. We detected a novel gene fusion between NUP98 and HOXA11 both in the chronic phase and in the acute leukaemia phase in this case. Although it is well known that a fusion of NUP98±HOXA9 in myeloid malignancies is created by the t(7;11)(p15;p15), this case suggests the possibility that HOXA11 might be another partner gene for NUP98 in t(7;11)(p15;p15) leukaemia.Keywords: CML, AML, NUP98, HOXA11, t(7;11).Translocation between chromosomal loci 7p15 and 11p15 was ®rst identi®ed in patients with Ph-negative chronic myeloid leukaemia (CML) (Kaneko et al, 1985), and this balanced translocation has recently been recognized to constitute a subset of acute myeloid leukaemia (AML) (Ohyashiki et al, 1987;Sato et al, 1987). Both Nakamura et al (1996) and Borrow et al (1996) demonstrated that the nucleoporin gene NUP98 is fused to HOXA9 by the t(7;11), and this fusion has thus been considered to be an essential genetic event for leukaemogenesis in patients with t(7;11), including AML (Borrow et al, 1996;Nakamura et al, 1996), Ph-positive CML (Yamamoto et al, 1999) and some patients with myelodysplastic syndromes (Hatano et al, 1999;Wong et al, 1999). We report here a patient with Ph-negative CML, but with t(7;11), who developed an acute leukaemia phase within a very short period. In this patient a novel fusion between NUP98 and HOXA11 was detected. CASE REPORTA 58-year-old Japanese woman was found to have leucocytosis and anaemia. Haematological ®ndings revealed the white blood cell (WBC) count to be 11á2´10 9 /l, including 0á5% metamyelocytes, 2á5% stab cells, 81á0% segmented cells, a haemoglobin (Hb) level of 10á0 g/dl, and a platelet count of 175´10 9 /l. Neither eosinophilia nor basophilia was present. A bone marrow aspirate revealed a hypercellular marrow (nucleated cell count of 1á386´10 12 /l) and myeloid hyperplasia (myeloid/erythroid ratio 26á1) with 7á2% myeloblasts, 10á4% promyelocytes, 26á8% myelocytes, 5á2% metamyelocytes, 28á0% stab cells and 15á6% segmented cells. Biochemical results were all within normal ranges, but serum vitamin B 12 was elevated (1800 ng/l) and there was a low level of neutrophil alkaline phosphatase (rate 27%, score 69). Chromosome study of the bone marrow cells revealed 46,XX,t(7;11)(p15;p15) in all 21 cells analysed. Based on the haematological data, the patient was diagnosed as Ph-negative CML with t(7;11). She was given hydroxyurea for about 1 month until admission owing to deterioration of haematological features.In October 2000, she was admitted to our hospital for re-evaluation of leukaemia. At this time, her WBC count was 40á3´10 9 /l, including 55% myeloblasts and 2% promyelocytes, a Hb level of 7á4 g/dl, and a platelet count of 68´10 9 /l. A bone marrow aspirate showed hypercelluar marrow with 84á5% myeloblasts and 5á6% promyelocytes. The blasts were positive for myelope...
458 Background: Both FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine(GnP) standard treatment in first-line treatment of metastatic pancreatic adenocarcinoma (MPA). It could be of interest to use them consecutively, knowing that there is currently no standard for second-line treatments for MPA. The aim of this study was to compare second-line modified FFX (mFFX) after GnP failure with second-line GnP after mFFX failure. Methods: From January 2015 to Jul 2017, medical records were retrospectively reviewed for consecutive patients receiving mFFX or GnP for a histologically proven MPA after failure of GnP or mFFX respectively. Patients were treated with mFFX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 h, no bolus 5-FU) or GnP (Gemcitabine 1000 mg/m2/, nab-paclitaxel 125mg/m2 d1,8 15) until disease progression, patient refusal or unacceptable toxicity. Results: Second-line mFFX was administered to 50 patients and GnP was 25 patients. At baseline of second-line treatment, there was no difference in patient’s characteristics between mFFX group and GnP group. No significant difference in the response rate (mFFX, 16.6% vs. GnP, 10.5%, P = 0.63) or the disease control rate (mFFX, 50% vs. GnP, 64%, P = 0.82) was seen between the two groups. Median Progression free survival of GnP/mFFx were 4.3 months/4.6 months (p=0.89) and median survival (OS) from the 2nd line treatment of GnP/mFFx were 10.4 months/10.8 months (p=0.65) and OS from the first-line treatment of GnP/mFFx were 20.6 months/16.5 months (p=0.34). No toxic death occurred in both groups. There was no difference in the incident of adverse event between mFFX group and GnP group. Conclusions: Second-line mFFX and GnP achieved similar disease control and survival in unresectable pancreatic cancer. The use of the FFX and GnP in sequence is an attractive option to maximize disease control and survival. We need the clinical trial to compare with mFFX and GnP in sequence to guide the selection of initial chemotherapy.
Interaction of a tyrosine kinase type receptor and its ligand induces receptor-dimerization or -oligomerization followed by transphosphorylation and activation of its intrinsic kinase, which leads to a series of intracellular signals. We have previously reported that the membrane-bound form of Steel factor (SLF) induces more persistent tyrosine kinase activation and longer life span of c-kit encoded protein (KIT) than its soluble form (Miyazawa et al, Blood 85:641, 1995). In this study, we used YB5.B8 monoclonal antibody (MoAb) that recognizes the extracellular domain of KIT to investigate whether immobilized anti-KIT MoAb can substitute for SLF as a potent activator of KIT by cross-linking receptors and further compared its effect with each SLF isoform in a factor-dependent cell line M07e. YB5.B8 MoAb in a soluble state suppressed SLF-induced M07e cell proliferation in a dose- dependent manner. By contrast, once this antibody was immobilized on the goat-antimouse MoAb (GAM)-coated culture plates, it supported the growth of M07e cells in the absence of any growth factors, whereas culture the cells in GAM alone or YB5.B8 without GAM-coated plates resulted in rapid cell-death within 24 hours. As with the natural ligand SLF, immobilized YB5.B8 MoAb synergized with granulocyte- macrophage colony-stimulating factor (GM-CSF) in inducing cell proliferation compared with either YB5.B8 MoAb or GM-CSF alone. Immunoblotting with antiphosphotyrosine MoAb showed that interaction of M07e cells with immobilized YB5.B8 induced tyrosine phosphorylation of a series of intracellular proteins including KIT (145 kD). In addition, cross-linking studies using a water-soluble cross linking reagent bis- sulfosuccinimidyl-suberate showed that immobilized YB5.B8 MoAb induced dimerization and activation of KIT. However, as with stimulation by the membrane-bound form of SLF, the kinetics of KIT activation with YB5.B8 MoAb was more prolonged compared with the cells treated with recombinant soluble SLF. Flow cytometry showed that, unlike the cells treated with soluble SLF, no downmodulation of cell-surface KIT expression was observed in M07e cells cultured with immobilzed YB5.B8 MoAb. These data suggest that immobilized antibodies against hematopoietic receptors may replace their ligand-stimulators; however, their activities may resemble the membrane-bound form rather than the soluble form of natural ligands.
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