RESUMO
BACKGROUND: Mast cell leukemia (MCL) is the most aggressive form of systemic mastocytosis disorders. Owing to its rarity, neither pathogenesis nor standard treatment is established for this orphan disease. Hence, we tried to treat a patient with MCL based on the exome and transcriptome sequencing results of the patient's own DNA and RNA. METHODS: First, tumor DNA and RNA were extracted from bone marrow at the time of diagnosis. Germline DNA was extracted from the patient's saliva 45 days after induction chemotherapy and used as a control. Then, we performed whole-exome sequencing (WES) using the DNA and whole transcriptome sequencing (WTS) using the RNA. Single nucleotide variants (SNVs) were called using MuTect and GATK. Samtools, FusionMap, and Gene Set Enrichment Analysis were utilized to analyze WTS results. RESULTS: WES and WTS results revealed mutation in KIT S476I. Fusion analysis was performed using WTS data, which suggested a possible RARα-B2M fusion. When RNA expression analysis was performed using WTS data, upregulation of PIK3/AKT pathway, downstream of KIT and mTOR, was observed. Based on our WES and WTS results, we first administered all-trans retinoic acid, then dasatinib, and finally, an mTOR inhibitor. CONCLUSION: We present a case of orphan disease where we used a targeted approach using WES and WTS data of the patient. Even though our treatment was not successful, use of our approach warrants further validation.
Assuntos
Humanos , Medula Óssea , Diagnóstico , DNA , Exoma , Medicina de Precisão , Quimioterapia de Indução , Leucemia , Leucemia de Mastócitos , Mastócitos , Mastocitose Sistêmica , Doenças Raras , RNA , Saliva , Transcriptoma , Tretinoína , Regulação para Cima , DasatinibeRESUMO
No abstract available.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Sequência de Bases , Medula Óssea/patologia , Análise Mutacional de DNA , Éxons , Imunofenotipagem , Leucemia de Mastócitos/diagnóstico , Mutação , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-kit/genéticaAssuntos
Humanos , Masculino , Feminino , Leucemia de Mastócitos/diagnóstico , Imunoterapia/métodos , Criança , Anafilaxia/sangue , Antígenos , LactenteRESUMO
In up to 40% of systemic mastocytosis (SM) cases, an associated clonal hematological non-mast cell lineage disease such as AML is diagnosed before, simultaneously with, or after the diagnosis of SM. A 40-yr-old man was diagnosed with AML with t(8;21)(q22;q22). Mast cells were not noted at diagnosis, but appeared as immature forms at relapse. After allogeneic hematopoietic stem cell transplantation (HSCT), leukemic myeloblasts were not observed; however, neoplastic metachromatic blasts strikingly proliferated during the state of bone marrow aplasia, and finally, aleukemic mast cell leukemia developed. As the disease progressed, we observed serial morphologic changes from immature mast cells with myeloblasts to only metachromatic blasts and atypical mast cells as mast cell leukemia; FISH analysis showed that the neoplastic mast cells originated from the same clone as the leukemic myeloblasts of AML.
Assuntos
Adulto , Humanos , Masculino , Células da Medula Óssea/patologia , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Transplante de Células-Tronco Hematopoéticas , Hibridização in Situ Fluorescente , Leucemia de Mastócitos/diagnóstico , Leucemia Mieloide Aguda/complicações , Leucócitos Mononucleares/patologia , Mastocitose Sistêmica/diagnóstico , Recidiva , Translocação Genética , Transplante HomólogoRESUMO
Se presenta el caso de un paciente masculino de 18 años con diagnóstico de leucemia granulocítica crónica con tres años de evolución en su fase crónica y desarrollo de crisis blástica con presencia de blastos con caracterización basofílica (basofiloblastos), positivos a las tinciones citoquímicas de azul de tolouidina y peroxidasa. A su ingreso se le demostró un cariotipo 46XY Ph-1+ y en la crisis blástica presentó trisomía de los romosomas 8 y 9, presencia de isocromosoma del brazo largo del 17, pérdida del cromosoma Y en algunas células, y persistencia del cromosoma Ph1+. Con todos estos datos clínicos y de laboratorio se concluyó el diagnóstico de leucemia basofílica secundaria a LGC con diferenciación basófilo-mieloblástica no descrita con anterioridad. Se hace una breve revisión de la literatura sobre esta rara variedad de leucemia