Search

Although blasts were increased in the bone marrow, they showed morphologic evidence of monocytic differentiation (Fig 1J), which was not prominent at diagnosis (Fig 1I) and was favoured to represent a differentiation response to IDH2i therapy. Patient 2 also showed a decline in donor chimaerism with IDH2i treatment and continues therapy with improving BME studies. Isocitrate dehydrogenase inhibitor-driven differentiation may resemble secondary graft failure in post-allogeneic haematopoietic cell transplantation relapsed acute myeloid leukaemia These cases, of two consecutive patients treated at our institution, illustrate the successful use of IDHi therapy on donor/recipient chimaerism and caution against the use of applying traditional parameters in evaluating treatment response. [Extracted from the article]

Aims Anaplastic lymphoma kinase ( ALK) functions as an oncogenic driver in a subset of haematopoietic, epithelial and mesenchymal neoplasms. Activation of ALK most commonly occurs through gene fusion events, the presence of which predicts response to ALK-targeted inhibitors in some tumour types. Echinoderm microtubule-associated protein-like 4 ( EML4)- ALK fusions represent the majority of ALK rearrangements in lung adenocarcinomas and were, until recently, thought to be exclusive to that tumour type. However, recent work has identified EML4- ALK fusions in ~20% of inflammatory myofibroblastic tumours ( IMTs), particularly in those arising in the lung. Here, we present a patient with an ALK-rearranged poorly differentiated lung adenocarcinoma with a predominant sarcomatoid component that was morphologically indistinguishable from IMT. Methods and results Targeted next-generation sequencing revealed EML4- ALK rearrangements in both components, with identical fusion sequences. Copy number analysis demonstrated focal gain of the MYC gene in the IMT-like component. The findings support a diagnosis of ALK-rearranged lung adenocarcinoma with IMT-like dedifferentiation. Conclusions Our findings suggest that ALK-driven epithelial and mesenchymal neoplasms exist on a morphological spectrum, and emphasize the need to consider translocation testing in pulmonary tumours with unusual sarcomatoid morphology. [ABSTRACT FROM AUTHOR]

Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. NPM1 is one of the most common recurrently mutated genes in AML. NPM1 mutations often co-occur with FLT3-ITDs and mutations in genes regulating DNA methylation, such as DNMT3A, TET2, and IDH1/2. It remains unclear whether these genetic alterations are associated with distinct immunophenotypic findings or affect prognosis. We identified 133 cases of NPM1-mutated AML and correlated sequencing data with immunophenotypic and clinical findings. Of 84 cases (63%) that lacked monocytic differentiation ("myeloid AML"), 40 (48%) demonstrated an acute promyelocytic leukemia-like (APL-like) immunophenotype by flow cytometry, with absence of CD34 and HLA-DR and strong myeloperoxidase expression, in the absence of a PML-RARA translocation. Pathologic variants in TET2, IDH1, or IDH2 were identified in 39/40 APL-like cases. This subset of NPM1-mutated AML was associated with longer relapse-free and overall survival, when compared with cases that were positive for CD34 and/or HLA-DR. The combination of NPM1 and TET2 or IDH1/2 mutations along with an APL-like immunophenotype identifies a distinct subtype of AML. Further studies addressing its biology and clinical significance may be especially relevant in the era of IDH inhibitors and recent work showing efficacy of ATRA therapy in NPM1 and IDH1-mutated AML., (© 2017 Wiley Periodicals, Inc.)