Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation.

Acute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = <0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(-) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97-14.2); p < 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.

[Role of leptin in eating disorders--current concept]. / Rola leptyny w zaburzeniach odzywiania sie --wspólczesne poglady.

Eating disorders constitute a dynamically developing group of diseases, in which only some have well-established diagnostic criteria, e.g. anorexia nervosa or bulimia nervosa. Many symptoms of eating disorders are hard to be qualified to any known disorder from that group, and quantity and diversity of symptoms connected to eating grow systematically. It makes the work of clinicians and psychotherapists more difficult, as well as hampers communication between specialists. It is also a challenge for scientists to create new qualifications based on known and theoretical pathomechanisms connected to disruptions in food intake regulation.

Inferior performance on selected neuropsychological tests in abstinent schizophrenia patients who have used cannabis.

BACKGROUND: A substantial proportion of patients with schizophrenia have co-morbid psychoactive substance use, which can influence their cognitive functions. The aim of this study was to assess cognitive functioning in abstinent schizophrenia patients with various previous patterns of psychoactive substance use. MATERIAL/METHODS: The study was performed on a group of 80 schizophrenia patients (74 men, 6 women), aged 18-40 (mean 25) years, of whom in 40 a co-morbid psychoactive substance abuse was diagnosed. The latter group was subdivided, based on their predominant type of substance (opioid, amphetamine, or cannabis). All patients were examined during clinical improvement, and patients with comorbid substance use were also examined after a 6-week period of detoxification in a therapeutic community. A battery of neuropsychiatric tests was used, which included subtests of Trail Making test, Stroop test and Verbal Fluency test. RESULTS: No significant differences in clinical factors and cognitive functioning between the 2 examined groups were found. However, when the patients were divided according to their pattern of substance use, it turned out that the group of patients who used cannabis, despite the shortest duration of disease and that of addiction, and highest percentage of using atypical antipsychotics, performed worse on all cognitive tests, significantly so on Stroop and Fluency tests, compared to the groups with predominant opioid or amphetamine use. CONCLUSIONS: Abstinent schizophrenic patients who previously used cannabis have worse cognitive functioning compared to other schizophrenic patients with comorbid substance use. The possible role of previous cannabis use or cannabis withdrawal in this phenomenon is discussed.

Imatinib mesylate may induce long-term clinical response in FIP1L1-PDGFRα-negative hypereosinophilic syndrome.

The idiopathic hypereosinophilic syndrome (HES) comprises a heterogenous group of disorders characterized by marked blood eosinophilia with eosinophilia-associated organ damage. Eight patients with a median age at diagnosis of 42 years (range 19-67) received imatinib mesylate (IM) for FIP1L1-PDGFRα-negative HES resistant to previous conventional treatment. Median number of prior therapies was 3 (range 2-4). Median time from diagnosis to IM initiation was 112 months (range 2-293). Four patients were treated daily with 100 mg IM, whereas the remaining four patients were treated daily with 400 mg IM. Four male patients (50%) achieved complete haematologic response (CHR) after median of 7 days (range 3-150) using 100 mg daily IM (n = 2) and 400 mg (n = 2). Median duration of IM treatment for IM responders was 18 months (range 2-88). No adverse events were reported throughout the treatment duration. Two patients maintained CHR while on 100 mg weekly IM. Four patients (2 men and 2 women) failed IM treatment. Median duration of IM for non-responding patients was 3 weeks (range 3-12). Non-responding HES patients were significantly older and had lower percentage of blood eosinophilia when compared with IM responders. Our results suggest that IM, even at lower than conventional doses, may induce and maintain long-term remission for FIP1L1-PDGFRα-negative HES.

Plasma levels of leptin and orexin A in the restrictive type of anorexia nervosa.

OBJECTIVE: The aim of the study was to analyze the pattern of leptin and orexin A plasma levels in patients with the restrictive type of anorexia nervosa (AN-R), during the course of treatment. Thirty females with AN-R, aged 18.0 ± 1.6 years (mean ± SD), range of 15.5-21.0 years, were investigated before and after 2, 3, and 6 months of treatment, which included a normocaloric diet and cognitive-behavioral psychotherapy. The control group consisted of 20 age-matched, healthy control females. RESULTS: Before the therapy, both leptin and orexin A plasma levels were significantly lower than in the control group and were negatively correlated. During treatment, leptin levels increased and, after 6 months, showed a correlation with body mass index (BMI). Orexin A levels showed a further decrease during treatment, with no correlation with BMI. CONCLUSIONS: The results corroborate those of other researchers showing a decrease of leptin levels in patients with AN-R and its increase with body mass increment. They may also suggest a possible relationship between leptin and orexin A plasma level patterns in such patients.

Cellular signal transduction pathways by leptin in colorectal cancer tissue: preliminary results.

The aim of the study was to analyse genes typing with the use of the oligonucleotide microarray technique (HG-U133A, Affymetrix) differentiating colorectal cancer tissues from tissues assessed histopathologically as healthy ones among a panel of 91 mRNA of genes encoding proteins involved in activation of cellular signal transduction pathways by leptin. Frozen tumor specimens from 11 colon cancer patients in various stages of clinical progression of the disease in an I-IV stage scale according to the TNM staging were used in molecular tests. Among the genes participating in the cascade of signal transfer in cell activated by leptin, the following ones: AKT1, STAT3, MCL1 were qualified as differentiating stage I and II and VEGFC, CCNDI the encoding genes respectively as differentiating III and IV stage neoplasm. It is necessary to extend studies of analysis of cellular signal transduction pathways by leptin in colorectal cancer initiation and transformation processes.

Bright light treatment of depressive symptoms in patients with restrictive type of anorexia nervosa.

BACKGROUND: Light therapy refers to two different categories of treatment. One of them is used in common medical practice and the other in complementary medicine. The aim of the study was to assess the effect of short time (6 weeks) bright light treatment (BLT) on depressive symptoms in female patients with the restrictive type of anorexia nervosa (AN-R). METHODS: Twenty-four girls, aged 15-20 (mean 17.4±1) years, diagnosed as AN-R, with concomitant depressive symptoms ≥17 points on the 21-item Hamilton Depression Rating Scale (HDRS) were studied. All girls received cognitive behavioral therapy. Among them, twelve were randomly assigned to additional treatment with BLT for 6 weeks (10,000 lux, 30 min daily). Both groups did not differ on baseline demographic and clinical parameters. The assessments of depression by means of HDRS and measuring of body mass index (BMI) were done weekly throughout the treatment. RESULTS: Improvement of depression was significantly greater in the group receiving BLT, with a significant difference between groups in depression intensity after 5 and 6 weeks. There was no difference in the increase of BMI between groups after 6 weeks, although such increase started earlier in patients treated with BLT. LIMITATIONS: Six weeks of treatment may be an insufficient duration to draw the conclusion about the efficacy of BLT and a follow-up is needed to assess the maintenance of the effect. CONCLUSIONS: The results obtained may suggest that BLT could be an effective non-pharmacological modality for the treatment of depression in patients with AN-R.

Expression profile of significant immortalization genes in colon cancer.

Cancer is a disease of genomic instability, a multistep process involving numerous mutations and chromosomal aberrations. Telomeres are highly specialized structures at the ends of chromosomes and function to stabilize and protect the ends of linear chromosomes, therefore determining cellular immortalization. Homeostasis of telomere length is a multifactor-dependent process. Since cellular immortalization is an early and essential step towards cancer, the aim of the present study was to determine immortalization genes that are significant in colon cancer and assess their usefulness in the early diagnosis of this tumor. Expression profiles of 119 transcripts known to be involved in cellular immortalization were assessed with oligonucleotide microarrays in 13 probes of colon adenocarcinoma (low and high clinical stages) and 9 probes of controls (normal colon tissue) and were compared among these groups with the use of the Significant Analysis Microarray (SAM) software and independently verified with the effect size parameter. Eighteen genes with significantly differential expression between high clinical stage colon cancer and the control group, and 21 with differential expression between low clinical stage colon cancer and the control group were identified. Nine genes showing altered expression in both low and high clinical stage colon cancer: ACD (TPP1), DKC1 and ERCC1, MYC, MAX, NBN, NOLA2, PRKDC and HSP82 should, in particular, be the subjects of further studies including QRT-PCR methods.

Preliminary study of the expression of genes connected with the orexigenic and anorexigenic system using microarray technique in anorexia nervosa.

The pathogenesis of anorexia nervosa (AN) is still poorly understood. The Diagnostic and Statistical Manual of Mental Disorders (4th edition) classification differentiates 2 AN types: the restricting type (AN-R) and the binge eating/purging type (AN-BP). We investigated 4 young women suffering from AN (2 with AN-R and 2 with AN-BP). Four women, age matched, with other psychiatric disorders (paranoid schizophrenia, adjustment disorder, mental retardation) served as the reference group. The oligonucleotide microarray method (HG-U133A, Affymetrix) was used to determine the expression profile of 13 genes connected with the orexigenic and anorexigenic system: leptin, leptin receptor-coding gene, hypocretin (orexin) receptor-coding gene, hypocretin (orexin) neuropeptide precursor-coding gene and growth hormone secretagogue receptor. A hierarchical analysis of the results showed that AN-BP and AN-R patients were grouped into different clusters. Also, expression levels of leptin receptor-coding gene showed significant differences between AN-BP and AN-R patients and between AN-R and control subjects. This preliminary study suggests that the microarray technique may contribute to elucidating molecular genetics of the pathogenesis of both types of AN.

[Anorexia nervosa with regard to oligonucleotide microarray technique--own data]. / Jadlowstrqt psychiczny w aspekcie mikromacierzy oligonukleotydowych--badania wlasne.

AIM: The aim of the study was to discover the transcript expression profile of selected genes coding receptors of leptin and orexin A and B by using the oligonucleotide microarray technique (Affymetrix, HG-U133A) in patients who suffered from anorexia nervosa (AN). METHOD: The peripheral blood of mononuclear cells (PBMC) of four AN patients complying with the ICD-10 and the AN diagnostic criteria DSM IV were analysed. Two patients suffered from the restricting type of AN (AN-R) and two suffered from the binge-eating/ purging type of AN (AN-BP). Four patients were our reference group and they did not suffer from eating disorders. The material used in the assay was the total RNA which was isolated from the PBMC of patients. The total RNA was used to investigate the transcript expression profile of selected genes by using the oligonucleotide microarray technique (Affymetrix, HG-U133A). For six and for eight oligonucleotide microarrays, the accumulation analysis method was used (clustering, Cluster v 3.0) to analyse the results. RESULTS: Hierarchical clustering resulted in separate clusters for patients who suffered from AN-R, AN-BP and patients from the reference group. CONCLUSIONS: Taking into consideration the hierarchical clustering for six and for eight oligonucleotide microarray performing different transcript expression profile of selected genes coding orexigenic peptides (OXA and OXB) and anorexigenic peptides (LEP) we suggest that the oligonucleotide microarray method differentiates two type of anorexia nervosa: the restricting type of AN (AN-R) and the binge-eating/purging type (AN-BP).

The transcript expression profile of the leptin receptor-coding gene assayed with the oligonucleotide microarray technique--could this be an anorexia nervosa marker?

Anorexia nervosa is a serious eating disorder with the highest mortality rate of any psychiatric disorder. The DSM-IV classification differentiates two AN types: the restricting type (AN-R) and the binge-eating/purging type (AN-BP). Leptin (LEP) levels can be thought of as a signal to the body of its energy reserves. The leptin receptor (including all its mRNA isoforms) is expressed in many tissues. Our aim was to discover the transcript expression profile of the LEP receptor-coding gene in the peripheral blood mononuclears in AN-R and AN-BP patients. Three young women suffering from Anorexia nervosa (one with AN-BP and two with AN-R) took part in the study, along with three non-anorexic subjects as our reference group. LEP receptor gene expression was examined using the oligonucleotide microarray method (HG-U133A, Affymetrix). The results were normalized using RMAExpress. Next, the accumulation analysis method was used (clustering). Hierarchical clustering resulted in three groups of separate clusters. The first group (cluster I) consisted of AN-R patients. The next group (cluster II) consisted of reference group patients suffering from different psychic disorders not related to eating disorders. Cluster III consisted of two patients--the first with AN-BP and the second with an adaptive disorder.