ABSTRACT
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5'-KMT2A, two patients had a 5'-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.
Subject(s)
Histone-Lysine N-Methyltransferase , Leukemia, Myeloid, Acute , Myeloid-Lymphoid Leukemia Protein , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Leukemia, Myeloid, Acute/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Histone-Lysine N-Methyltransferase/genetics , Myeloid-Lymphoid Leukemia Protein/genetics , Gene FusionABSTRACT
BACKGROUND: Diffuse sclerosing osteomyelitis (DSO) of the mandible is characterized by mixed bone resorption and formation. METHODS: Immunohistopathology of DSO in the clinically acute and subacute phases was compared with healthy bone. RESULTS: Receptor activator of nuclear factor kappaB ligand (RANKL) was found in DSO lesions. When it was used in vitro to stimulate monocytes, cathepsin K expression was observed in mononuclear prefusion precursors and in multinuclear giant cells. Similarly, exacerbations of DSO were characterized by RANKL and induction of cathepsin K in mononuclear precursor cells, which subsequently seem to differentiate into osteoclasts or foreign body giant cells. The proportion of bone to soft tissue increased with the duration of disease. CONCLUSIONS: RANKL-driven osteoclastogenesis and acidic cysteine endoproteinase cathepsin K seem to play important roles in DSO as osteoclast-mediated bone resorption may represent the primary disease process later followed by new bone formation.
Subject(s)
Bone Resorption/metabolism , Cathepsins/analysis , Mandibular Diseases/metabolism , Osteomyelitis/metabolism , RANK Ligand/analysis , Adolescent , Adult , Aged , Animals , Case-Control Studies , Cathepsin K , Female , Goats , Horses , Humans , Male , Mandibular Diseases/pathology , Mice , Middle Aged , Osteoclasts/cytology , Osteomyelitis/pathology , RabbitsABSTRACT
Diffuse sclerosing osteomyelitis (DSO) of the mandible is a chronic condition, the cause of which is not known. Jaw pain, occurring irregularly, is a typical symptom. The aim of the study was to assess the effectiveness of disodium clodronate for relieving pain in patients with DSO. Disodium clodronate is a bisphosphonate used to treat diseases of bone and calcium metabolism. Ten DSO patients experiencing pain received disodium clodronate or placebo intravenously on a randomized double-blind basis. Both minimum (300 mg) and maximum (900 mg) doses were well tolerated. Disodium clodronate administration did not result in better immediate pain relief than placebo administration. However, 6 months after treatment there was a statistically significant difference in pain intensity between the groups, with the disodium clodronate group experiencing significantly less pain.
Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Clodronic Acid/administration & dosage , Facial Pain/drug therapy , Mandibular Diseases/drug therapy , Osteomyelitis/drug therapy , Adult , Aged , Analysis of Variance , Chronic Disease , Double-Blind Method , Facial Pain/etiology , Female , Humans , Injections, Intravenous , Male , Mandibular Diseases/complications , Middle Aged , Osteomyelitis/complications , Pain Measurement , Statistics, Nonparametric , Treatment OutcomeSubject(s)
Acquired Hyperostosis Syndrome/diagnosis , Acquired Hyperostosis Syndrome/drug therapy , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azithromycin/therapeutic use , Female , Glucocorticoids/therapeutic use , Humans , Prednisone/therapeutic use , Treatment OutcomeABSTRACT
Three papers were presented in the session focusing on educational approaches: Anu Narusk reported on an Estonian study on the influence of the family on adolescents' substance use, Bernadette Roussille presented a French mass media campaign aimed at reducing heavy drinking by young people, and Sally Casswell analysed the public discourse on alcohol, which is an important part of the social and political context in which decisions are taken about public policies. Each of the papers highlighted in its own way the complex relationships between people's behaviour, its social and cultural context, and the wider economic and political environment.
Subject(s)
Alcohol Drinking/epidemiology , Health Education , France , Humans , Socioeconomic FactorsSubject(s)
Alcoholism/prevention & control , Health Policy , Mass Media , Adolescent , Adult , Advertising , Alcohol Drinking , Alcoholism/psychology , Child , Female , Health Education , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Research , TelevisionABSTRACT
Thirty-four patients with mandibular diffuse sclerosing osteomyelitis who had been treated by means of 61 decortications were evaluated retrospectively. Eighteen patients (53%) were free from symptoms on an average of 5.4 years after surgery. Of these, 12 had improved after their first operation. In the other six patients, decortication was performed two to four times before healing was clinically observable. Symptoms recurred in 75% of the cases within 12 months after surgery. Neither sex, location, extent, and chronicity of the disease nor the precise surgical technique used seemed to affect the outcome. The patients who exhibited improvement, however, were significantly older and more often edentulous than the patients in whom the symptoms recurred. Possible causes of failure were an insufficiently radical surgical procedure and retention of devitalized teeth in the decorticated area.
