| 41. |
- Foster, Nicola, et al.
(author)
-
Molecular characterisation of a recurrent, semi-cryptic RUNX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukaemia
- 2010
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 148:6, s. 938-943
-
Journal article (peer-reviewed)abstract
- P>A proportion of cytogenetic abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) may escape detection by high-resolution genomic technologies, but can be identified by conventional cytogenetic and molecular analysis. Here, we report the detection of a reciprocal translocation t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH). Reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis identified a fusion between RUNX1 and the gene encoding ubiquitin specific peptidase-42 (USP42), with splice-variants and variable break-points within RUNX1. Combined cytomorphology and FISH studies in MDS marrow revealed abnormal RUNX1 signals within megakaryocytes, suggesting that the acquisition of t(7;21)(p22;q22) does not confer complete differentiation arrest and may represent an early genetic event in leukaemogenesis. Single nucleotide polymorphism-arrays failed to detect additional sub-microscopic genomic changes predisposing to or associated with t(7;21). Molecular analysis of 100 MDS and AML marrow specimens by RT-PCR did not reveal new cases with the RUNX1-USP42 fusion. Thus, our studies have identified t(7;21)(p22;q22) as a rare but recurrent abnormality in MDS/AML, with the existence of alternative spliced forms of the RUNX1-USP42 transcript in different patients. Further studies are required to identify the potential contribution of these splice-variants to disease heterogeneity.
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| 42. |
- Fäldt, R., et al.
(author)
-
Inhibition of platelet aggregation by myeloid leukaemic cells demonstrated in vitro
- 1987
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 66:4, s. 529-534
-
Journal article (peer-reviewed)abstract
- The effect of myeloid leukaemic cells, cells of the promyelocytic cell line HL-60 and normal polymorphonuclear granulocytes (PMN), enclosed in dialysis tubes, on the aggregation of allogeneic normal platelets after induction with arachidonic acid (AA) and with adenosine diphosphate (ADP) was investigated in vitro. Inhibition of aggregation was seen after preincubation of the platelets with leukaemic blood or bone marrow cell from 7/14 patients belonging to various FAB groups and with HL-60, but not with normal PMN (14/14 cases). A dose-dependent inhibition was seen after lysis of some leukaemic cells with anti-human rabbit antiserum and active complement. Lysis of normal PMN inhibited platelet aggregation slightly and inconstantly and only at higher cell concentrations. Platelet inhibitory activity was not related to a higher rate of metabolism of the leukaemic cells which inhibited platelet aggregation with respect to heat production. Neither was a non-specifically increased cell membrane permeability the cause of the release of platelet inhibitory factor(s) since the release of 51Cr-labeled leukaemic cells was not related to the inhibition of platelet aggregation.
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| 43. |
- Geisler, Christian H., et al.
(author)
-
Nordic MCL2 trial update : six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur
- 2012
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
-
Journal article (peer-reviewed)abstract
- Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early based on the median observation time of 4 years results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6.5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7.4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL.
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| 44. |
- Green, P. M., et al.
(author)
-
Haemophilia B mutations in a complete Swedish population sample : a test of new strategy for the genetic counselling of diseases with high mutational heterogeneity
- 1991
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 78:3, s. 390-397
-
Journal article (peer-reviewed)abstract
- Carrier and prenatal diagnosis based on the identification of the gene defect (direct diagnosis) increases the proportion of haemophilia B families that can be offered precise genetic counselling from the 50-60% attainable by DNA markers, to 100%, and they also provide information on the molecular biology of the disease. We propose that in order to maximize the practical and scientific benefits of direct diagnosis the gene defect of complete (possibly national) populations of patients should be characterized and the information stored in appropriate confidential databases. We demonstrate the feasibility of such a strategy by characterizing the mutations of all the patients registered with the Malmo haemophilia centre. These patients (44♂ and 1♀) are from 45 unrelated families and 24 (53%) have negative family history. The 25 patients with similar reduction of factor IX:C and factor IX:Ag (24♂ + 1♀) have: two gross deletions, three frameshifts, four translation stops, six mutations expected to affect pre-mRNA splicing and 10 amino acid substitutions. The six patients with greater reduction of factor IX:C than factor IX:Ag and the seven with reduced IX:C and normal IX:Ag have only amino acid substitutions. Patients with inhibitors have: one complete deletion, one frameshift and three translation stops. One patient has both a translation stop and a functionally neutral amino acid substitution (His257→Tyr). Characterization of the factor IX mutation was successful in every case, usually entailed 4 person-days work, and has led to the identification of 12 amino acid residues essential for the factor IX structure and function.
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| 45. |
- Hemminki, Kari, et al.
(author)
-
Associated cancers in parents and offspring of polycythaemia vera and myelofibrosis patients
- 2009
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 147:4, s. 526-530
-
Journal article (peer-reviewed)abstract
- Polycythaemia vera (PV) and primary myelofibrosis (MF) show concordant familial clustering but limited population level data are available on the aggregation of other discordant neoplasms in these families. We used the Swedish Family-Cancer Database to assess risks for VP and MF in families of cancer patients. A total of 3530 first PV and 1606 MF patients were identified, with high concordant familial risks. Several discordant familial associations were found for PV (acute myeloid leukaemia, Hodgkin disease, prostate and bladder cancers) or for MF (chronic lymphatic leukaemia, colorectal, kidney and cervical cancers) or for both (nervous system, eye and endocrine tumours).
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| 46. |
- Holmberg, Lars, et al.
(author)
-
Bernard-Soulier syndrome Karlstad : Trp 498-->Stop mutation resulting in a truncated glycoprotein Ib alpha that contains part of the transmembranous domain
- 1997
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 98:1, s. 57-63
-
Journal article (peer-reviewed)abstract
- In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation. Trp 498-->Stop in the GPIb alpha gene, resulting in a truncated GPIb alpha polypeptide chain. In contrast to previously reported truncated forms of GPIb alpha, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIb beta. Flow cytometry with GPIb alpha antibodies demonstrated the presence of GPIb on the patient's platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIb alpha of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIb alpha lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.
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| 47. |
- Linderoth, Johan, et al.
(author)
-
Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma
- 2008
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 141:4, s. 423-32
-
Journal article (peer-reviewed)abstract
- In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.
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| 48. |
- Lindqvist, Pelle, et al.
(author)
-
The relationship between lifestyle factors and venous thromboembolism among women: a report from the MISS study.
- 2009
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 144, s. 234-240
-
Journal article (peer-reviewed)abstract
- There has been a great advance in our knowledge of the role that thrombophilic factors play in the risk of venous thromboembolic events (VTE). However, the effect of lifestyle factors on VTE has been inadequately explored in large scale studies of women. This cohort study comprised one thousand native Swedish women for each age year between 25 and 64 inclusive (total = 40 000) drawn from the South Swedish population registry for 1990 (n = 40 000), who were followed for a mean of eleven years. Seventy-four percent completed a questionnaire at the inception of the study (n = 29 518) and 24 098 women responded to a follow-up inquiry between the years 2000-2002. The main outcome was the relationship between VTE and physical exercise, smoking habits, and alcohol consumption. Moderate drinkers of alcohol (10-15 g/d) and women engaged in strenuous exercise were at half the risk of VTE compared to those who consumed little or no alcohol or lived a sedentary life. Heavy smoking was associated with a 30% increased risk of VTE. Lifestyle factors have a major impact on the risk of VTE. Women non-smokers who were physically active and who consumed alcohol in moderation were at a lower risk of VTE.
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| 49. |
- Ljung, Rolf
(author)
-
The risk associated with indwelling catheters in children with haemophilia.
- 2007
-
In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 138:5, s. 580-586
-
Research review (peer-reviewed)abstract
- Infections are the most frequent complications associated with the use of central venous lines (CVLs) in children with haemophilia. Several retrospective studies that include data from a substantial number of patients have reported approximately 0.2-0.3 infections per 1000 catheter-days (mainly Port-A-Cath). Some studies have shown a much higher frequency of infections, 1-2/1000 catheter-days. The most plausible explanations, for the difference seen in frequency of infections with Port-A-Caths, are probably related to the protocol used for the device care and the quality of education and the compliance of the users, whether these are parents or health-care professionals. The figures are low for clinically apparent thrombosis in the larger series on record, but routine venograms were not performed in most of these series. In studies, where this has been performed, a high frequency of abnormalities (> 50%) on venograms have been seen in some series but not in others. Despite obvious potential risks with CVLs, they are useful in many cases and facilitate the treatment of a serious disorder. With careful guidelines and surveillance protocols, the risk of complications should be reduced in the future.
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| 50. |
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