Abstract:
:A clonal origin of hematopoiesis was studied by investigation of X-chromosome inactivation patterns (XCIP) in isolated granulocyte, CD14(+) and CD3(+) subpopulations obtained from bone marrow and peripheral blood of 36 female patients with primary myelodysplastic syndrome (MDS). Clonality was assessed by PCR amplification of polymorphic short tandem repeats of the human androgen receptor (HUMARA) gene and by investigation of silent polymorphism of iduronate sulphatase (IDS) or p55 genes. On the basis of results in a control group of 20 healthy age related females, a ratio of at least 9:1 between the two alleles was considered a significant marker of monoclonal hematopoiesis. Ten of the 11 patients with advanced forms of MDS (RAEB, RAEB-T, CMML) had clonal granulocytes and CD14(+) cells in peripheral blood. In patients with early disease, only 2 out of 11 patients (18%) with RA or RARS, according to WHO classification, had clonal granulocytes and CD14(+) cells in peripheral blood and bone marrow and 2 other patients with 5q-syndrome exhibited extremely oligoclonal granulocyte subpopulation in bone marrow. In contrast, we found clonal granulocytes in 12 out of 14 patients (86%) with refractory cytopenia with multilineage dysplasia (RCMD) and 8 of them simultanously exhibited clonal CD14(+) cells. Estimated 3 years survival of patients with early disease and clonal cell subpopulations was 61% as compared with 88% in patients without clonal hematopoiesis. Karyotype abnormalities were detected in 11 of the 25 females with early disease. Clonal patterns were present in 7 out of 8 patients with abberations diagnosed by routine cytogenetics, nevertheless, FISH revealed 5q deletion in 3 patients without signs of clonality in XCIP assay. No correlation was found between the presence of clonal subpopulations and the degree of telomere shortening in early MDS. Despite some limitations, the measurement of XCIP remains a sensitive tool for diagnosis of the first transforming mutation in the clonal development of MDS especially when combined with FISH and when an age related group is used to establish an appropriate allele ratio to exclude constitutional or acquired skewing. The occurrence of clonal cell subpopulations in most of the RCMD patients in contrast to RA may reflect a proposed multistep pathogenesis of MDS with dysplastic changes limited to erythropoiesis in early step and with subsequent development of multilineage dysplasia. The results also support the usefulness of separation of RCMD from 'pure' RA; however, a more complex insight combining different molecular techniques performed in a large number of patients is needed for refined classification of MDS on the basis of new molecular prognostic factors and for indication of more effective targeted therapy.
journal_name
Leuk Resjournal_title
Leukemia researchauthors
Cermák J,Belicková M,Krejcová H,Michalová K,Zilovcová S,Zemanová Z,Brezinová J,Sieglová Zdoi
10.1016/j.leukres.2004.08.008keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
371-9issue
4eissn
0145-2126issn
1873-5835pii
S0145-2126(04)00303-0journal_volume
29pub_type
杂志文章abstract:BACKGROUND:Chylomicrons carry in the bloodstream dietary fats absorbed the intestine for storage in the body tissues such as adipose and muscle. The two-step chylomicron metabolism consists in lipolysis by lipoprotein lipase on vessel walls and hepatic uptake of triglyceride-depleted remnants. Chylomicron metabolism is...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(02)00087-5
更新日期:2003-02-01 00:00:00
abstract::The inaugural meeting of the International Working Group on MDS cytogenetics convened 22-23 October 2007 in Chicago, IL. Under the sponsorship of the Myelodysplastic Syndromes Foundation, the group was organized to address the substantial need for worldwide standardized cytogenetic testing for MDS in clinical practice...
journal_title:Leukemia research
pub_type: 总体
doi:10.1016/j.leukres.2008.03.009
更新日期:2008-09-01 00:00:00
abstract::Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(00)00045-x
更新日期:2000-09-01 00:00:00
abstract::Smoking may be associated with accelerated erythropoiesis, leukocytosis and thrombocytosis, which are also hallmarks in patients with polycythemia vera, essential thrombocythemia and early stages of myelofibrosis (MPNs). The JAK-STAT and NF-κB signaling pathways are activated in both smokers and in patients with MPNs....
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2015.09.002
更新日期:2015-09-09 00:00:00
abstract::An acute promyelocytic leukemia in the rat (BNML) has been used in model studies on pathogenesis and therapy of human acute myeloid leukemia. The blood supply to bone marrow during BNML development has hitherto not been examined, even though in general, blood flow to hematopoietic tissues might affect drug treatment a...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90071-r
更新日期:1993-08-01 00:00:00
abstract::The usefulness of a new method to detect B-cell monoclonality named VR, which is a combination of the digestion with restriction enzymes and vectorette PCR, in aspiration biopsy-nucleic acid diagnosis (ABND) of thyroid malignant lymphoma was investigated. ABND was performed in 12 patients in whom malignant lymphoma wa...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.03.019
更新日期:2008-01-01 00:00:00
abstract::We have recently established the MV4-11 acute myelogenous leukemia (AML) subline, designated as MV4-11 TP53 R248W, which possesses a missense mutation (CGG→TGG; R248W) in the TP53 gene, leading to inactivation of this transcription factor. DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-AzadC) induced...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2011.04.004
更新日期:2011-07-01 00:00:00
abstract::Like CD19 or CD56, CD22 in non-lymphoid leukemia has been considered an aberrantly expressed antigen. CD22 had been believed to be restricted to B lymphoid, however, it was also found to be expressed in human basophils. Mature basophils are unique granulocytes expressing CD13, CD22 and CD25. To estimate whether the ex...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2003.10.034
更新日期:2004-07-01 00:00:00
abstract::We investigated the effects of two sex steroids (17beta estradiol and testosterone) on five human leukemia cell lines. We observed a statistically significant inhibition of proliferation, dose and time dependent, of the human monoblastic leukemia cell line U937. This inhibition was associated with a dose dependent dec...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(98)00101-5
更新日期:1998-11-01 00:00:00
abstract::It has been suggested that imatinib mesylate (IM) influences osteogenesis and bone turnover in treated patients. Here we show that the inhibitory effect of IM on cell multiplication is associated with an increased proportion of spliced osteocalcin (OCNs) in leukemia (HL-60) and osteosarcoma cells (MG-63, U-2 OS), desp...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2007.07.020
更新日期:2008-03-01 00:00:00
abstract::Defective apoptosis is a hallmark of the progression of B chronic lymphocytic leukaemia (B-CLL). Smac-mimetics have been shown to induce apoptosis in several tumours. We describe the in vitro pro-apoptotic activity and regulation of the molecular pathway induced by new Smac-mimetics in B-CLL. The cytotoxic effect was ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2013.03.016
更新日期:2013-07-01 00:00:00
abstract::The association between seven polymorphisms in the genes hOCT1 and MDR1, encoding for imatinib transporter proteins, and the response to imatinib 400mg/daily was investigated in 65 patients newly diagnosed with chronic-phase chronic myeloid leukemia. The AA genotype at the rs6935207 hOCT1 polymorphic locus was not det...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2010.12.004
更新日期:2011-08-01 00:00:00
abstract::1,25-Dihydroxyvitamin D3 (1,25D) induces differentiation of myeloid leukemia cells, but resistant cells are also encountered. We studied the mechanistic basis for the resistance in a model system using enhancers of 1,25D, the antioxidant carnosic acid and a kinase inhibitor SB202190. Knock-down (KD) of JNK2p54 unexpec...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.03.003
更新日期:2009-10-01 00:00:00
abstract::Activating mutations or over-expression of the Flt3 is prevalent in acute myeloblastic leukemia (AML), associated with activation of Ras/MAP kinase and other signaling pathways. In this study, we addressed the role of Flt3 in the activation of nuclear factor-kappa B (NF-kappaB), which is a target molecule of these kin...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2005.01.008
更新日期:2005-08-01 00:00:00
abstract::Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associa...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(98)00192-1
更新日期:1999-05-01 00:00:00
abstract::The prognostic relevance of 12p deletion is controversial in multiple myeloma (MM) and the status of 12p deletion is unknown in other plasma cell disorders. We investigated 12p deletion in 88 patients with MM, 19 patients with monoclonal gammopathy of undetermined significance (MGUS), and 17 patients with plasma cell ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2011.07.030
更新日期:2012-01-01 00:00:00
abstract::Internal tandem duplications (ITDs) of the FLT3 gene occur in approximately 20-30% of acute myeloid leukemia (AML) patients. We investigated if FLT3 ITDs could be used as minimal residual disease (MRD) markers for AML patients. Patient-specific polymerase chain reaction (PCR) assays for FLT3 ITDs were developed for fo...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(01)00087-x
更新日期:2001-12-01 00:00:00
abstract::The effect of mesna on intracellular accumulation of cytosine arabinoside (Ara-C) in murine normal and neoplastic lymphocytes was studied. Simultaneous exposure of cells to mesna at concentrations ranging from 0.25 to 1.0 mM and 3H-Ara-C (40.0 nM) resulted in a strong inhibition of Ara-C uptake in normal lymphocytes. ...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(93)90117-4
更新日期:1993-09-01 00:00:00
abstract::A patient with myelodysplastic syndromes (MDS) developed eosinophilia during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). To study the mechanism of this eosinophilia, we investigated the proliferation of eosinophil colony-forming units (CFU-Eo) in nine patients and four...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/0145-2126(95)00083-6
更新日期:1995-12-01 00:00:00
abstract::Blastic transformation of myeloproliferative neoplasms (MPN) is still poorly understood. We describe a cohort of 23 Roswell Park Cancer Institute (RPCI) patients and 89 additional cases from the English literature for whom biologic features were described. We initially compared our 23 patients to the 89 cases from the...
journal_title:Leukemia research
pub_type: 杂志文章,评审
doi:10.1016/j.leukres.2010.07.031
更新日期:2011-05-01 00:00:00
abstract::We evaluated the cytotoxicity of dimethylsphingosine (DMS) against four human leukemia cell lines: two acute (HL60 and a multi-drug resistance MDR-positive derivative HL60-dox) and two blast crisis chronic myelogenous leukemias (JFP1, from a treatment refractory patient and K562), and against blasts isolated from 11 l...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(01)00129-1
更新日期:2002-03-01 00:00:00
abstract:BACKGROUND:Myeloid sarcoma is a tumor mass that consists of myeloblasts or immature myeloid cells at an extramedullary site. Pathological diagnosis is very difficult based on morphology if systemic signs of disease are absent. The subtype of myeloid sarcoma is also minimally identifiable in the histological picture. F...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2016.01.002
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:Better risk-stratification of patients with chronic lymphocytic leukemia (CLL) and identification of subsets of ultra-high-risk (HR)-CLL patients are crucial in the contemporary era of an expanded therapeutic armamentarium for CLL. METHODS:A multivariate patient similarity network and clustering was applied...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::A double monoclonal component (MC) detected in the serum and/or urine represents a very rare occurrence (2-6% of monoclonal gammopathies). In this study, we report 34 patients with double serum MCs, focusing on the associated diseases. The diagnosis was made using high-resolution serum protein electrophoresis and immu...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2012.05.008
更新日期:2012-10-01 00:00:00
abstract::The expression of various proto-oncogenes in primary culture of lymphocytes from peripheral blood of bovine with chronic lymphocytic leukemia (CLL) was studied. Cellular proto-oncogenes encode proteins that propagate growth, differentiation or apoptosis signals from cell membrane to nucleus. The proliferation and diff...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/s0145-2126(97)00128-8
更新日期:1998-02-01 00:00:00
abstract::Osteopontin (OPN) is a cytokine that contributes substantially to the growth and metastasis in a wide spectrum of malignancies. We report here that OPN gene is transactivated by Tax protein of human T-cell leukemia virus type 1 (HTLV-1). Northern blot showed enhanced OPN gene expression in cells stably expressing Tax....
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2009.08.028
更新日期:2010-06-01 00:00:00
abstract::Discovering genetic predictors of childhood acute lymphoblastic leukemia (ALL) necessitates the evaluation of novel factors including maternal genetic effects, which are a proxy for the intrauterine environment, and robust epidemiologic study designs. Therefore, we evaluated five maternal and offspring xenobiotic meta...
journal_title:Leukemia research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.leukres.2013.01.020
更新日期:2013-05-01 00:00:00
abstract:INTRODUCTION:The seven in absentia homolog 2 (SIAH2) protein plays a significant role in human cancer by regulating hypoxia-inducible factor-a (HIF-1α); however, its role in T-cell acute lymphoblastic leukemia (T-ALL) is less clear. METHODS:Immunofluorescence evaluation of SIAH2 protein expression and location were co...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2016.01.013
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND/AIMS:Jumping translocations are rare cytogenetic aberrations in haematological malignancies, the pathogenesis of which remains to be fully characterised. We investigated the mechanism of formation of jumping translocations in a case of adult common acute lymphoblastic leukaemia (ALL) positive for the Ph tran...
journal_title:Leukemia research
pub_type: 杂志文章
doi:10.1016/j.leukres.2004.01.021
更新日期:2004-10-01 00:00:00
abstract::We evaluated outcomes in two consecutive groups of AML patients age>60 years in CR after 7+3 induction therapy. Group 1 received consolidation with cytarabine 1.5g/m(2) q12h×6+daunorubicin for two cycles, while group 2 received consolidation with 7+3 followed by mitoxantrone+etoposide. For patients with intermediate-r...
journal_title:Leukemia research
pub_type: 临床试验,杂志文章
doi:10.1016/j.leukres.2013.01.001
更新日期:2013-05-01 00:00:00