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N Hamajima

Publications and source records attributed to N Hamajima.

At least 55 records · Page 3Linked to original sources
PubMed2001

No substantial difference in genotype frequencies of interleukin and myeloperoxidase polymorphisms between malignant lymphoma patients and non-cancer controls.

BACKGROUND AND OBJECTIVES: The functional polymorphisms regulating immunologic responses may influence the proliferation or suppression of malignant lymphoma. We examined the association between malignant lymphoma risk and the polymorphisms of the IL-1 gene family [IL-1B -31 C/T, IL-1A -889 C/T, and IL-1RN 86-bp variable number of terminal repeat (VNTR)] and myeloperoxidase (MPO -463 G/A). DESIGN AND METHODS: The hospital-based case-control study was conducted in Japan. Genotypes were examined in a total of 372 lymphoma cases and 241 non-cancer control subjects. The relative risks were estimated by unconditional logistic regression analysis. RESULTS: The overall allele distribution of these polymorphisms did not differ substantially between patients and controls; the odds ratios were 0.73 (95% confidence interval, 0.48-1.11) for the T allele carriers of IL-1B relative to the non-carriers, 1.01 (0.56-1.82) for the 2-repeat allele (allele 2) carriers of IL-1RN, 0.96 (0.62-1.48) for the T allele carriers of IL-1A, and 1.04 (0.70-1.57) for the A allele carriers of MPO. Subgroup analyses according to histology [diffuse large B-cell lymphoma (DLBL), follicular lymphoma, low-grade lymphoma of mucosa associated lymphoid tissue, and others] failed to illustrate differences except for DLBL which showed a possible association with IL-1A and IL-1B polymorphisms. INTERPRETATION AND CONCLUSIONS: Our data show a limited association between these polymorphisms and malignant lymphoma risk in total. The possible association of the IL-1A and IL-1B polymorphisms with DLB-needs further clarification.

Adolescent↗
PubMed2001

Polymorphisms of two fucosyltransferase genes (Lewis and Secretor genes) involving type I Lewis antigens are associated with the presence of anti-Helicobacter pylori IgG antibody.

Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and Lewis (Le) gene are involved in type I Le antigen synthesis. The present study was performed to investigate the possibility that Se and Le gene polymorphisms alter the risk of H. pylori infection. Two hundred thirty-nine participants were genotyped for Se and Le and tested for the presence of anti-H. pylori IgG antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we assessed immunohistochemically whether type I Le antigen expression depended on the Se and Le genotypes. The H. pylori infection rate was positively associated with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se group, 73.3%) and negatively associated with the number of Le alleles (le/le group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were classified into three groups [low risk, (se/se, Le/Le) genotype; high risk, (Se/Se, le/le), (Se/Se, Le/le), and (Se/se, le/le) genotypes; moderate risk, other than low- or high-risk group], the odds ratio relative to the low-risk group was 3.30 (95% confidence interval, 1.40-7.78) for the moderate-risk group and 10.33 (95% confidence interval, 3.16-33.8) for the high-risk group. Immunohistochemical analysis supported the finding that Se and Le genotypes affected the expression of H. pylori adhesin ligands. We conclude that Se and Le genotypes affect susceptibility to H. pylori infection.

Adult↗
PubMed2001

[Association between the interleukin 1B (C-31T) polymorphism and Helicobacter pylori infection in health checkup examinees].

PURPOSE: Associations between Helicobacter pylori (HP) infection and lifestyle factors have been demonstrated by several studies, but there are very few reports on links with host factors, especially concerning genetic polymorphisms for inhabitants of large city. The present investigation was conducted to determine the HP infection rate with reference to the Interleukin-1 beta gene (IL-1B) polymorphism and assess the interactions with smoking reported for outpatients. METHOD: The subjects were 468 participants in a health-check-up program of law of health for aged conducted by Nagoya Nishi Health Center. The participants were asked to permit use of their residual blood drawn during a health-check-up program and written informed consent was obtained for gene polymorphism tests. Data on smoking habit were obtained by self-administered questionnaire. The IL-1B C-to-T polymorphism at -31 was genotyped by PCR-CTPP (polymerase chain reaction with confronting two-pair primers) and an anti-HP IgG antibody test was used for detecting HP infection. Differences in values were assessed by a chi 2 test. An unconditional logistic model was applied for estimating odds ratios with the computer program STATA Version 6. This study was approved by the Ethical Committee at Aichi Cancer Center in 2000 before it was commenced (Ethical Committee Approval Number 11-12) RESULTS: The HP infection rate was 52.6% (61/116) for the C/C genotype of IL-1B-31, 48.6% (89/183) for the C/T, and 63.2% (103/163) for T/T; the difference were not statistically significant. However, when non-current smokers were excluded, the rate were 47.8% (11/23), 52.9% (18/34), and 72.7% (16/22), respectively, indicating the T/T genotype to have a higher infection rate. The age-sex-smoking adjusted odds ratio (OR) relative to the C/C genotype were 0.97 (95% confidence interval, 0.59-1.57) for the T/C genotype and 1.73 (1.04-2.87) for the T/T genotype. Among current and former smokers the age-sex adjusted OR were 1.68 (0.50-5.71) for the T/C genotype and 5.29 (1.11-25.1) for the T/T genotype, suggesting a effect of this polymorphism prominent in smokers. CONCLUSION: An association between the IL-1B-31 polymorphism and persistent HP infection was observed for inhabitants with a smoking habit, indicating that this polymorphism is one genetic trait conferring an increased likelihood of persistent HP infection.

Adult↗
PubMed2000

Cloning and characterization of the Caenorhabditis elegans CeCRMP/DHP-1 and -2; common ancestors of CRMP and dihydropyrimidinase?

The vertebrate CRMP (collapsin-response-mediator protein) gene family comprises at least four members. These CRMPs exhibit about 60% amino acid identity with vertebrate dihydropyrimidinase (DHP), an amidohydrolase involved in the pyrimidine degradation pathway. CRMP is also referred to as DRP (DHP-related protein), TOAD-64 (turned on after division, 64 kDa) and Ulip (Unc-33-like phosphoprotein). These vertebrate CRMPs are expressed mainly in early neuronal differentiation, which suggests that they play a role in neuronal development. In this study we isolated two cDNA clones from nematode C. elegans based on their sequence homology to vertebrate CRMPs and DHP. These two molecules, termed CeCRMP/DHP-1 and -2, turned out to be Ulip-B and -A, respectively, which were previously identified in the C. elegans genomic database by Byk et al. (1998). These newly isolated molecules were believed to represent a common ancestral state before the gene duplication between CRMPs and DHP. CeCRMP/DHP-1 and -2 protein retained all putative zinc-binding residues thought to be essential for the amidohydrolase activity of DHP and exhibited a weak amidohydrolase activity when 5-bromo-dihydrouracil was used as a substrate. Whole-mount in situ hybridization and expression analysis using GFP fusions revealed that CeCRMP/DHP-1 was transiently expressed in the hypodermis of C. elegans during the early larva stage. CeCRMP/DHP-1 was also expressed in a single nerve cell between the pharynx and ring neuropil. On the other hand, expression of CeCRMP/DHP-2 was observed in the body wall muscle throughout the lifespan of C. elegans. These results indicate that a major site of CeCRMP/DHP-1 and -2 expression is non-neuronal. Targeted gene disruption of CeCRMP/DHP-2 caused no particular difference in appearance or movement phenotype.

Amidohydrolases↗
PubMed2000

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Adolescent↗
PubMed2000

Comparison of lifestyle and risk factors among Japanese with and without gastric cancer family history.

To find specific risk factors of gastric cancer (GC) independent of GC family history (GCFH), 2 studies were conducted using the database of the Hospital-based Epidemiological Research Program at Aichi Cancer Center: (i) a comparison of lifestyles between non-cancer cases with positive and negative GCFH status and (ii) a case-reference investigation of subjects with and without GCFH, treated separately. The first showed no significant variation of GCFH status with regard to smoking, drinking and most food habits. Multivariate analyses in the case-referent studies revealed odds ratios (ORs) for GC associated with habitual smoking of 2.78 (95% CI 1.22-6.28) for those with and 2.74 (95% CI 1.76-4.26) for those without GCFH. In individuals with GCFH, an independently lowered OR (0.52, 95% CI 0.27-0.99) was evident for frequent consumption of raw vegetables, whereas the opposite was noted for pickled vegetables (2. 39, 95% CI 1.28-4.45). No statistically significant interaction was found between GCFH and selected lifestyle items. In conclusion, our results suggest a limited influence of GCFH on risk factors for GC.

Adult↗
PubMed2000

Neurofibrillary tangle-associated collapsin response mediator protein-2 (CRMP-2) is highly phosphorylated on Thr-509, Ser-518, and Ser-522.

3F4, a monoclonal antibody raised against partially purified paired helical filaments (PHFs), strongly labeled neurofibrillary tangles and some plaque neurites but barely labeled neuropil threads. The levels of the 65-kDa antigen were significantly increased in the soluble fraction of the brains affected by Alzheimer's disease (AD), as compared with that in the case of control brains. The antigen was previously identified as human collapsin response mediator protein-2 (hCRMP-2) by sequencing the immunoaffinity-purified 65-kDa antigen [Yoshida, H., Watanabe, A., and Ihara, Y. (1998) J. Biol. Chem. 273, 9761-9768]. Here, we show that the 3F4 antigen represents a highly phosphorylated form of CRMP-2. The 3F4-reactive phosphoepitope was localized to the carboxyl-terminal portion of hCRMP-2, and was created by a novel 45-50-kDa protein kinase in rat brain extract. Site-directed mutagenesis of this portion showed that multiple sites of CRMP-2 are differentially phosphorylated within residues 507-522, and that phosphorylation of three sites, Thr-509, Ser-518, and Ser-522, is required for full 3F4 binding. The phosphorylation of this particular portion carboxyl-terminal to the basic region of CRMP-2 may play an important role in regulating its activity, and may be involved in the formation of degenerating neurites in AD brain.

Alzheimer Disease↗
PubMed2000

SEREX analysis of gastric cancer antigens.

Stomach cancer is the major malignancy in Japan and one of the most common cancers worldwide. To establish the basis for an immunotherapeutic approach to stomach cancer, we have initiated an analysis of stomach cancer antigens recognized by human immunoglobulin G (IgG) antibodies using SE-REX, a powerful expression cloning method developed by Dr. M. Pfreundschuh's group. Five stomach cancer cDNA libraries have been screened with autologous patient sera: one moderately differentiated adenocarcinoma; two poorly differentiated adenocarcinomas; and two scirrhous-type poorly differentiated adenocarcinomas of Borrmann type 4, the most devastating form of stomach cancer. Based on the reactivities of clones with autologous IgG antibodies, an average of 50 independent clones from each library and a total of 297 clones were isolated. DNA sequencing revealed that these 297 clones were derived from 136 different genes. Comparison of the 136 genes to sequences in DNA databases showed that 95 are previously identified genes and 41 are newly identified in this study. The antigens are derived from various genes including a chimeric gene between E-cadherin and an unknown gene Y, AKT oncogene, genes overexpressed in stomach cancers, genes of which the transcripts are alternatively or aberrantly spliced, and genes known to be involved in autoimmune diseases. Thus stomach cancer patients can generate an immune response against a surprisingly diverse set of gene products. To identify antigens potentially useful in the diagnosis and therapy of gastric cancer, all 136 genes were tested for their reactivities with a panel of sera from 44 gastric cancer patients (17 women and 27 men, aged 35-81 years) and with a panel of sera from 100 control individuals with no previous history of cancer but some of whom had gastritis (55 women and 45 men, aged 30-69 years). Eleven antigens showed reactivity only with a certain proportion of cancer patient sera but not with any control sera. An additional 12 antigens elicited antibody production at a much higher frequency in cancer patients than in control individuals. To evaluate the clinical usefulness of these antigens we are now examining their expression in normal and malignant tissues.

Adult↗
PubMed2000

Differential expression of dihydropyrimidinase-related protein genes in developing and adult enteric nervous system.

Dihydropyrimidinase-related proteins (DRPs) are involved in axonal outgrowth and pathfinding. However, little is known about their significance in the enteric nervous system (ENS), the largest and most complex division of the peripheral nervous system. Using in situ hybridization (ISH) and northern blotting, we examined mRNA expression of DRP-1-4 transcripts in the developing and adult mouse digestive tract and in the adult human colon. ISH detected the mouse DRP-3 transcript in the developing ENS on embryonic day (E)12 and at the later stages as well as in the adult intestine. Mouse DRP-1 and -2 transcripts appeared at E14. DRP-2 transcript was also detected in the adult intestine although DRP-1 expression was lower in the adult. DRP-4 gene was not expressed in the ENS during development or adulthood whereas the signal was apparent in the developing and adult central nervous system (CNS). The DRP expression pattern in the human colon was similar to that of the mouse large intestine. Northern blot analysis showed that DRPs were differentially expressed in the mouse and human intestines, supporting the results of ISH. These data suggest that DRPs play a role not only in the CNS but also in the ENS.

Adult↗
PubMed2000

Subsite-specific risk factors for hypopharyngeal and esophageal cancer (Japan).

OBJECTIVES: To clarify subsite-specific risk factors for hypopharyngeal and esophageal cancers (HC and EC), we concluded a hospital-based case-referent study in Nagoya, Japan. METHODS: Subjects comprised 346 male cases with cancer of the hypopharynx (n = 62) or esophagus (upper [U-EC] 53, middle [M-EC] 159, lower [L-EC] 72), and 11,936 male referents free from cancer among first-visit outpatients aged 40-79 years in 1988-1997. Of histological confirmed cases, 93% comprised squamous cell carcinoma. Odds ratios (ORs) were estimated by a logistic regression model with adjustment for potential confounding factors. RESULTS: Cigarette smoking increased the OR for M-EC, and alcohol drinking elevated the ORs for all subsites. The trend of ORs for combined cases of M- and L-EC tended to increase with number of cigarettes (p = 0.056), and a decreasing trend of the ORs was found with years after quitting smoking (p = 0.006). The ORs for smoking with drinking were multiplicatively greater than those for smoking or drinking in combined cases of HC and EC. In contrast, daily raw vegetable consumption lowered the ORs for all subsites. CONCLUSIONS: This study suggests that the magnitude of risk with smoking is stronger for M-EC within the esophagus, and drinking increases the risk at any subsite.

Adult↗
PubMed2000

Hospital capacity and post-transplant survival after allogeneic bone marrow transplantation: analysis of data from the Japan Society for Hematopoietic Cell Transplantation.

The association between hospital capacity and survival after allogeneic bone marrow transplantation (allo-BMT) was examined using the dataset accumulated by the Japan Society of Hematopoietic Cell Transplantations (JSHCT). The subjects were 3134 patients who received first allo-BMTs between 1991 and 1997 reported to the JSHCT. They were divided into three groups by cumulative hospital experience of allo-BMTs: low volume (capacity) (LV; < or = 25 cases), moderate volume (capacity) (MV; 26-75 cases) and high volume (capacity) (HV; > or = 76 cases). Using a proportional hazards model, the association of hospital experience with early survival at day 100 (D100S), and overall survival (OS) were examined. For leukemia patients, leukemia-free survival (LFS) was also analyzed. When HV was defined as the reference group, the hazard ratios (HRs) of OS for all subjects were 1.10 (95% confidence interval; 0.97-1.25) for MV and 1.25 for LV (1.08-1.44). The HRs with D100S were 1.20 (0.96-1.51) for MV and 1.40 (1.08-1.80) for LV. Larger values were observed for OS and D100S in cases of leukemia. Survival after BMT from sibling donors was clearly influenced by hospital experience, but this was not the case from unrelated donors. These findings suggest that size of the transplant team should be considered in order to improve the outcome of sibling BMT in general.

Adolescent↗
PubMed2000

Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan.

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon alpha (IFN-alpha) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN-alpha as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3.6 years from registration. The survival of responders (CR + PR) was significantly better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7-year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD-IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non-responders.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Polymerase chain reaction with confronting two-pair primers for polymorphism genotyping.

A novel PCR method using confronting two-pair primers, named PCR-CTPP, is introduced to detect a single nucleotide polymorphism (base X or Y). One primer for the X allele is set to include X' at the 3' end (antisense), where X' is the antisense of X, with the counterpart sense primer upstream. For the Y allele, a sense primer including Y at the 3' end is set, with the antisense primer downstream. One common band and one specific band for each allele are amplified, which allows genotyping directly by electrophoresis. This method is exemplified by application to the polymorphisms of beta-adrenoceptor 2 and interleukin 1B. It is simpler than PCR-RFLP (restriction fragment length polymorphism), which requires incubation with a restriction enzyme, and is suitable for genotyping in studies of genetic epidemiology involving hundreds of samples.

Genotype↗
PubMed2000

No association of the 5' promoter region polymorphism of CYP17 with breast cancer risk in Japan.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.

Adult↗
PubMed2000

Effects of dietary, drinking, and smoking habits on the prognosis of gastric cancer.

Although it has been clarified that dietary, drinking, and smoking habits contribute to the onset of gastric cancer, little is known about their impact on prognosis of gastric cancer. To examine this question, a prognostic analysis was conducted using data from Aichi Cancer Center Research Institute and Hospital. From January 1988 to December 1994, information on 877 gastric cancer patients (578 men and 299 women) regarding habitual smoking and drinking, food consumption, histological grade, and clinical stage of tumor as well as follow-up results were collected. Survival status of all patients was followed up until December 1998, and the survival function was estimated by the Kaplan-Meier method. Proportional hazard analysis was used to test the effect of each lifestyle item on gastric cancer death. After controlling for age, gender, histological grade, and stage of disease, hazard ratios (HR) were calculated. Values for consumption of raw vegetables [HR = 0.74, 95% confidence interval (CI) = 0.56-0.98], tofu (HR = 0.65, 95% CI = 0.42-0.99), and chicken meat (HR = 0.61, 95% CI = 0.39-0.95) more than three times per week demonstrated significantly decreased risk. However, the risk ratio was 2.53 (95% CI = 1.22-5.29) for habitual smokers, and an inverse dose-response relationship was also found between ever smoking and gastric cancer patient survival. Therefore, this study suggested that frequent intake of raw vegetables and tofu is favorable, whereas habitual smoking is an adverse prognostic factor for gastric cancer. Our study implies that an improvement of survival of Japanese gastric cancer might be achieved by lifestyle improvement.

Adenocarcinoma↗
PubMed2000

Depressive mood and suicide among middle-aged workers: findings from a prospective cohort study in Nagoya, Japan.

BACKGROUND: In Japan, mortality from suicide has peaked around 50 years old among men, with increasing trend after 65 years old, and this peak became more apparent in recent years. Beside this, "psychological autopsy" has revealed depression as one of the most important risk factors for suicide. There is, however, no cohort study which examined the relationship between depressive mood measured by simple method and suicide in middle-aged general population. METHODS: In 1989, baseline information was collected by a self-administered questionnaire, and 18,450 workers were followed up to March 31, 1995. All deaths observed during active service were identified, and when retired, its date was recorded. Among 5,352 male workers aged between 40 to 54, 11 committed suicide during follow-up period of 5 years. Analysis were carried out by Cox's proportional hazard model, controlling for age. RESULTS: Those who slept 9 hours or more per night demonstrated 12.14-fold risk of suicide compared with those who slept less than 9 hours. Smokers were more likely to commit suicide than non-smokers. Those who answered affirmatively to more than 7 out of 12 questions, which were derived from Zung self-rating depression scale, experienced an increased risk of suicide (RR 9.95; 95%CI: 1.89-52.44), even after adjusting for other confounding factors. CONCLUSION: We found an association between depressive mood and subsequent suicide in a middle-aged workers. Detailed observation and follow-up of those with depressive mood should be systematically organized with due attention and caution.

Adult↗
PubMed2000

Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors.

It is known that alkylating agents and topoisomerase II inhibitors can cause distinct forms of therapy-related leukemia and myelodysplastic syndrome (TRL/MDS). Although several reports have been made on each of these agents separately, no study has yet been conducted to evaluate the effect of these two types of agents in the same population. In a nationwide, large-scale population study, the clinical and cytogenetic features as well as the prognostic factors in 256 patients with TRL/MDS were assessed. Median age was 61 years, and the median period of latency from primary malignancies was 47.9 months. The latency period was significantly shorter in patients undergoing chemotherapy, especially that of topoisomerase II inhibitors, for primary cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia in 59% and MDS in 41% of patients. Chromosome abnormalities that frequently involved chromosomes 5, 7 or 11 were documented in 77% of the 189 patients examined. MLL gene rearrangements were detected in 11 of 58 subjects and were correlated with a borderline significance (P = 0.072) with topoisomerase II inhibitor administration. Overall median survival was only 9.7 months. Survival was similar in cases with or without MLL gene rearrangement. Multivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, poor therapy outcomes for primary cancer, C-reactive protein, and thrombocytopenia as being significantly poor prognostic factors (P < 0.05). This large-population study provided a comprehensive update of TRL/MDS status in Japan, identified significant prognostic factors, and enabled the clinical significance of MLL gene rearrangement to be assessed.

Adult↗