Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.
© 2024. The Author(s).

Acute promyelocytic leukemia (APL) during pregnancy is rare and difficult to treat. To the best of our knowledge, there is little precedent for successful treatment with combined chemotherapeutic agents without affecting delivery. The present study reported the case of a 31-year-old woman pregnant with twins who presented to the antenatal service at 13-week gestational age with complaints of vaginal bleeding, lower abdominal pain, bleeding gums and skin ecchymosis, and was eventually diagnosed with APL. After treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO)-based induction regimen, the patient achieved a complete remission (CR) and delivered two healthy male infants at 34 weeks of gestation. The use of ATRA and ATO for the treatment of APL is controversial due to teratogenic effects and lethal retinoic acid syndrome. However, the patient demonstrated that the chemotherapy regimen with ATRA and ATO during the second and third trimesters can result in a sustainable remission and successful pregnancy outcome.
Copyright © 2020, Spandidos Publications.

Measurable (minimal) residual disease (MRD) in B-acute lymphoblastic leukemia (B-ALL), as assessed by flow cytometry, is an established prognostic factor used to adjust treatment in most pediatric therapeutic protocols. MRD in B-ALL has been standardized by the Children's Oncology Group in North America and more recently in a multicenter Foundation for the National Institutes of Health-funded study. This article outlines the reagents, instrument setup, and analysis protocols required for the reproducible detection of residual leukemic cells in patients following induction therapy for B-ALL. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Staining and flow cytometry for B-acute lymphoblastic leukemia (B-ALL) measurable residual disease detection Support Protocol: Specimen collection, handling, storage, and shipping Basic Protocol 2: Analysis and interpretation of data for B-ALL measurable residual disease detection Basic Protocol 3: Analysis of samples lacking sufficient CD19+ events.
© 2022 Wiley Periodicals LLC.

Here, we describe a protocol for reprogramming of bone marrow-derived multipotent mesenchymal stromal/stem cells to obtain induced pluripotent stem cells from patients with primary immune deficiencies using lentiviral vectors, followed by hematopoietic differentiation of the MSC-derived iPSCs. This protocol is particularly helpful in cases where it is difficult to obtain sufficient numbers of hematopoietic cells for research and can be applied to model any hematological/immunological disease.
© 2021. Springer Science+Business Media, LLC.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The MMRF CoMMpass study is a longitudinal, observational clinical study of newly diagnosed multiple myeloma patients where tumor samples are characterized using whole genome, exome, and RNA sequencing at diagnosis and progression, and clinical data is collected every three months. Analyses of the baseline cohort identified genes that are the target of recurrent gain- and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high- risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.