generation-expansion-primary-malignant-pleural-mesothelioma-tumor

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Current methodologies for the expansion of primary tumor cell lines from rare tumor types are lacking. This protocol describes methods to expand primary ...

University of Texas MD Anderson Cancer Center

The concurrent presence of JAK2 V617F, monocytosis, and bone marrow fibrosis can be observed in both chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (PMF). It can be challenging to distinguish CMML with JAK2 mutation and fibrosis from other myeloid neoplasms, particularly PMF. To identify key features that may help distinguish these 2 entities, we retrospectively studied 21 cases diagnosed as "CMML" with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed in 2006 to 2016. Upon further review, we confirmed the diagnosis of CMML in 7 cases, 11 cases were reclassified as PMF, and 3 cases had features intermediate between CMML and PMF (gray zone). These 11 cases of PMF with monocytosis featured a higher JAK2 V617F allelic burden (median, 43%; range, 20%-62%) and atypical pleomorphic megakaryocytes with hyperchromatic nuclei. Complete blood count showed more pronounced myeloid left shift. In contrast, 7 CMML cases had significantly lower JAK2 V617F allelic burden (median, 17%; range, 5%-36%; P < .0001) and dysplastic megakaryocytes along with variable degree of dysplasia in other lineages. The median survival of PMF and CMML patients was 32 and 40 months, respectively. We conclude that besides morphology of megakaryocytes and other features, JAK2 V617F allelic burden can help differentiate CMML from PMF with monocytosis. SRSF2 and RAS mutations are observed in both disease categories. Rare gray-zone cases exist with hybrid features.

Utility of JAK2 V617F allelic burden in distinguishing chronic myelomonocytic Leukemia from Primary myelofibrosis with monocytosis.

Chimeric antigen receptor (CAR) T cells have emerged as a potent therapeutic approach for patients with certain haematological cancers, with multiple CAR T cell products currently approved by the FDA for those with relapsed and/or refractory B cell malignancies. However, in order to derive the desired level of effectiveness, patients need to successfully receive the CAR T cell infusion in a timely fashion. This process entails apheresis of the patient's T cells, followed by CAR T cell manufacture. While awaiting infusion at an authorized treatment centre, patients may receive interim disease-directed therapy. Most patients will also receive a course of pre-CAR T cell lymphodepletion, which has emerged as an important factor in enabling durable responses. The time between apheresis and CAR T cell infusion is often not a simple journey, with each milestone being a critical step that can have important downstream consequences for the ability to receive the infusion and the strength of clinical responses. In this Review, we provide a summary of the many considerations for preparing patients with B cell non-Hodgkin lymphoma or acute lymphoblastic leukaemia for CAR T cell therapy, and outline current limitations and areas for future research.

Carlos Ramos

Department of Translational Molecular Pathology

University of Texas MD Anderson Cancer Center

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Carlos Ramos

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Translational Molecular Pathology

University of Texas MD Anderson Cancer Center

Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines

Department of Translational Molecular Pathology