Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia.

Chemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown. Here we investigated the links between ABC activity, as evaluated by JC-1 +/- cyclosporine A assay, and immunophenotypic, cytogenetic, molecular, and targeted next-generation sequencing features in 361 AML patients. High ABC activity was found in 164 patients and was significantly associated with less proliferating disease, an immature immunophenotype (expression of CD34, HLA-DR, CD117, CD13), and gene mutations defining AML as belonging to secondary-type ontogenic groups. Low ABC activity was associated with more mature myeloid differentiation (CD34-, cyMPO+, CD15+, CD33+) or monocytic commitment (CD64+, CD4+weak, CD14+), with NPM1 mutations, KMT2A rearrangements, and core-binding factor gene fusions, hallmarks of the de novo-type AML ontogeny. ABC activity was one of the major factors we identified using a random forest model for early prediction of AML ontogeny. In the 230 patients evaluated at diagnosis and intensively treated, high ABC activity was a predictive factor for primary resistance, and in multivariate analysis including full molecular data, an independent factor for event-free survival (P=0.0370). JC-1 +/- cyclosporine A assay could be used at diagnosis to predict AML ontogeny and to complete prognosis evaluation in addition to new molecular markers.

Invasive Fungal Rhinosinusitis Due to Co-infection with Mucormycosis and Exserohilum rostratum in a Patient with Acute Lymphoblastic Leukemia.

Invasive fungal infections remain an important cause of complication and morbidity in the management of acute leukemias. Here we report the case of a 27-year-old patient from French Polynesia who was diagnosed with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. After induction chemotherapy, she developed rhinosinusitis with extensive bone lysis. The context and clinical presentation quickly made us suspect an invasive mucormycosis infection. However, a multidisciplinary investigation including mass spectrometry techniques also revealed the presence of Exserohilum rostratum, a pathogen member of the genus Exserohilum that is ubiquitous in tropical and subtropical regions but rarely implicated in invasive sinusitis. Antifungal treatment combined with an early surgical approach resulted in a favorable clinical response.

Good's syndrome and IgA monoclonal gammopathy of undetermined significance.

Characterised by the association of a thymoma, hypogammaglobulinaemia, and B-cell and T-cell dysfunction, Good's syndrome (GS) is a rare cause of adult immunodeficiency leading to recurrent infections, and autoimmune manifestations related to the thymoma. We describe a 70-year-old woman in whom the diagnosis of GS was made after 7 years follow-up of a monoclonal gammopathy of undetermined significance (MGUS). After thymectomy, she received monthly intravenous immunoglobulin perfusions in order to maintain a normal plasmatic IgG level. To our knowledge, this is the fifth described case of GS associated with an MGUS. This rare condition should not be misdiagnosed, as the prognosis is determined by infectious and autoimmune complications, which could be prevented.

[Histopathologic pattern of hyperplasia of bone marrow hematogones (medullar b lymphoid cell precursors) occurring after treatment of idiopathic myelofibrosis]. / Aspect histopathologique d'une hyperplasie médullaire osseuse des hématogones (précurseurs lymphoïdes B médullaires) au cours d'une myélofibrose idiopathique traitée.

Hematogones are bone marrow precursors of B-lymphoid cells which are morphologically difficult to distinguish from blasts and/or from small lymphocytes. We report the case of a patient presenting idiopathic myelofibrosis with minimal myeloid blastic transformation causing severe pancytopenia, treated by allograft and showing in a bone marrow biopsy, a hyperplasia of B-lymphoid cells. Histopathology and immunohistochemistry identified these cells as hyperplasia of hematogones and not a transformation into lymphoblastic acute leukaemia. The cytology of a myelogram confirmed the diagnosis.