RESUMEN
Due to the proliferation of genetic testing, pathogenic germline variants predisposing to hereditary hematological malignancy syndrome (HHMS) have been identified in an increasing number of genes. Consequently, the field of HHMS is gaining recognition among clinicians and scientists worldwide. Patients with germline genetic abnormalities often have poor outcomes and are candidates for allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using blood from a related donor should be carefully considered because of the risk that the patient may inherit a pathogenic variant. At present, we now face the challenge of incorporating these advances into clinical practice for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and optimizing the management and surveillance of patients and asymptomatic carriers, with the limitation that evidence-based guidelines are often inadequate. The 2016 revision of the WHO classification added a new section on myeloid malignant neoplasms, including MDS and AML with germline predisposition. The main syndromes can be classified into three groups. Those without pre-existing disease or organ dysfunction; DDX41, TP53, CEBPA, those with pre-existing platelet disorders; ANKRD26, ETV6, RUNX1, and those with other organ dysfunctions; SAMD9/SAMD9L, GATA2, and inherited bone marrow failure syndromes. In this review, we will outline the role of the genes involved in HHMS in order to clarify our understanding of HHMS.
Asunto(s)
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Genes Reguladores , Neoplasias Hematológicas/genética , Síndromes Mielodisplásicos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Células Germinativas , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Clinical use of gene panel testing for hematopoietic neoplasms in areas, such as diagnosis, prognosis prediction, and exploration of treatment options, has increased in recent years. The keys to interpreting gene variants detected in gene panel testing are to distinguish between germline and somatic variants and accurately determine whether the detected variants are pathogenic. If a variant is suspected to be a pathogenic germline variant, it is essential to confirm its consistency with the disease phenotype and gather a thorough family history. Donor eligibility must also be considered, especially if the patient's variant is also detected in the expected donor for hematopoietic stem cell transplantation. However, determining the pathogenicity of gene variants is often complicated, given the current limited availability of databases covering germline variants of hematopoietic neoplasms. This means that hematologists will frequently need to interpret gene variants themselves. Here, we outline how to assess the pathogenicity of germline variants according to criteria from the American College of Medical Genetics and Genomics/Association for Molecular Pathology standards and guidelines for the interpretation of variants using DDX41, a gene recently shown to be closely associated with myeloid neoplasms with a germline predisposition, as an example.
Asunto(s)
ARN Helicasas DEAD-box , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Hematológicas , Humanos , ARN Helicasas DEAD-box/genética , Pruebas Genéticas/métodos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/diagnóstico , Guías de Práctica Clínica como AsuntoRESUMEN
In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10-4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10-4. We propose this method as an effective MRD assay.
Asunto(s)
Citometría de Flujo , Cadenas kappa de Inmunoglobulina , Cadenas lambda de Inmunoglobulina , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B , Neoplasia Residual , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Neoplasia Residual/diagnóstico , Inmunofenotipificación/métodos , Citometría de Flujo/métodos , Femenino , Masculino , Cadenas Ligeras de Inmunoglobulina/metabolismoRESUMEN
Background: We aimed to clarify the predictive factors for left ventricular (LV) function after aortic valve replacement (AVR) in patients with aortic regurgitation (AR). Methods and results: Among 555 patients who underwent AVR at our institution from January 2015 to December 2020, we enrolled 44 patients for whom only AVR (or AVR + aortic replacement) was performed. We defined LV dysfunction under any of the following criteria: LV ejection fraction (LVEF) <50 %, LV diastolic dimension >65 mm, LV systolic dimension (LVDs) >50 mm, or LVDs/body surface area > 25 mm/m2. Multivariable logistic regression analysis revealed high natural logarithm (ln) C-reactive protein (CRP) and low LVEF in the pre-AVR period significantly associated with LV dysfunction after AVR (ln CRP: odds ratio [OR] 4.15, 95 % confidence interval [CI] 1.44-11.98, p < 0.01; LVEF: OR 0.79, 95%CI 0.65-0.97, p < 0.05). Receiver-operating characteristic analysis revealed an area under curve of CRP and LVEF in the pre-AVR period for LV dysfunction after AVR of 0.84 and 0.83, respectively. Upon dividing the patients into four groups according to cutoff values of CRP (0.13 mg/dL) and LVEF (50 %) in the pre-AVR period, no patients (0/19) had LV dysfunction in the low CRP (<0.13 mg/dL) and high LVEF (≥50 %) group, and all patients (5/5) in the high CRP (≥0.13 mg/dL) and low LVEF (<50 %) group had LV dysfunction after AVR. Conclusion: High CRP level was significantly and independently associated with LV dysfunction after AVR. Combination of CRP and LVEF values might be useful for predicting improvement in LV function after AVR.