Jeffrey Pu

Jeffrey Pu
The University of Arizona | UA · Department of Medicine

About

87
Publications
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1,824
Citations
Citations since 2017
48 Research Items
1626 Citations
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20172018201920202021202220230100200300400

Publications

Publications (87)
Article
Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes. We treated 13 bMCL patients with...
Article
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Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing...
Article
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The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of cyclin D1 through a chromosome t(11;14) translocation. MCL international prognostic index (MIPI), k...
Article
Background: Umbilical cord blood hematopoietic stem cell transplant (UCBT) has been practiced as an alternative source of hematopoietic stem cells for patients in need of transplantation. Double-units UCBT has been established as a means of achieving a cell dose of at least 2.5x10 7 nucleated cells per kilogram of body weight in adult recipients. T...
Article
Background Crovalimab is a novel anti-complement C5 antibody currently being studied as a treatment for paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disease associated with hemolytic anemia and thrombosis. Treatment with approved C5 inhibitors eculizumab or ravulizumab is effective, but can be limited by breakthrough hemolysis due...
Article
Background: Targeted therapies including ibrutinib, acalabrutinib and venetoclax (ven) have fundamentally changed the treatment of patients (pts) with chronic lymphocytic leukemia (CLL) leading to improved outcomes and durable remissions for many pts. However, CLL remains an incurable disease and a subset of pts will ultimately have progressive CLL...
Article
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Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpo...
Article
Full-text available
Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malig...
Article
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Immune thrombocytopenic purpura (ITP) is a hematological disorder characterized by immune-mediated destruction of platelets that could be triggered by a number of causes. ITPs are usually treated with steroid, immunomodulators or immunosuppressors, and intravenous immunoglobulin therapy though refractory/relapsed status frequently occurs. It was su...
Preprint
Full-text available
Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been previously linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assem...
Article
Purpose: Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in CLL. Umbralisib a novel, highly selective PI3Kδ/CK1ε inhibitor, is active and well tolerated in CLL patients. This phase 2 trial evaluated umbralisib in CLL patients who are intolerant to prior BTK or PI3K inhibitor therapy. Patients and methods: In this...
Article
Full-text available
Polyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3′-untr...
Article
Background Crovalimab is a novel anti-human complement component 5 (C5) antibody currently under investigation as a therapy for paroxysmal nocturnal hemoglobinuria (PNH), a life-threatening disorder characterized by hemolytic anemia and thrombosis. In the Phase I/II COMPOSER trial (NCT03157635; Röth et al. Blood. 2020), crovalimab showed promise as...
Article
Full-text available
Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we...
Article
Background Crovalimab is a novel anti-human complement component 5 (C5) antibody engineered to significantly extend half-life and enable subcutaneous (SC) administration once every 4 weeks in C5-mediated diseases. Based on the promising results of the Phase I/II COMPOSER trial (NCT03157635; Röth et al. Blood. 2020), crovalimab is currently under in...
Article
BACKGROUND: Treatment of chronic lymphocytic leukemia (CLL) with a fixed-duration venetoclax (Ven)-based regimen is now a standard of care (SOC) option for both frontline and relapsed refractory (R/R) disease based on results of the CLL14 and MURANO trials (Fischer et al NEJM 2019, Seymour et al NEJM 2018). As fixed-duration Ven regimens are now a...
Article
Full-text available
Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hu...
Article
Full-text available
Introduction: Recent randomized trials have demonstrated the efficacy of ibrutinib-based therapy in the treatment of patients with CLL. In Alliance A041202, a higher than expected number of unexplained deaths were reported with front-line ibrutinib in a patient population aged at least 65 years compared to ECOG 1912, which included patients up to...
Article
Full-text available
Given advanced age, comorbidities, and immune dysfunction, CLL patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease-19 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL p...
Article
Purpose: Venetoclax-based therapy is a standard of care option in front-line and relapsed/refractory CLL. Patient management following venetoclax discontinuation remains non-standard and poorly understood. Experimental design: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetocl...
Article
Full-text available
Abstract Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5–6% non-Hodgkin’s lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experime...
Article
Introduction: Venetoclax (VEN) based therapy has become a standard of care in front line and relapsed-refractory (R/R) CLL based on favorable efficacy and toxicity. Whereas prospective data regarding activity of therapies following ibrutinib (IBR) or idelalisib (IDE) are available in the settings of progression (VEN, non-covalent BTKi) and intolera...
Article
Hydroxyurea (HU) has been widely used in sickle cell disease. Its potential long-term risk for carcinogenesis or leukemogenic risk remains undefined. Here, we report a 26 y old African-American female with Sickle Cell Disease (SCD) who developed refractory/relapsed acute myeloid leukemia (AML) 6 months after 26 months of HU use. That patient’s cyto...
Article
Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non‐Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vori...
Article
Full-text available
This pilot study compared outcomes of patients with severe myelofibrosis (MF) who received pre- and post-SCT Rux (Cohort A), pre-SCT Rux only (Cohort B), and never received Rux (Cohort C), between 6/2012 and 6/2017. The study consisted of 16 patients, 11 male and 5 female, with a median age of 59 years at the time of SCT. The MF scores ranged from...
Article
Introduction: Mantle cell lymphoma (MCL) is a malignancy of monomorphic small to medium-sized B lymphocytes and is considered incurable with standard chemotherapy. Median survival estimates are three to seven years, with even shorter survival times in patients with the blastoid variant and with higher proliferation rates. A number of chemotherapy...
Article
Ibrutinib demonstrated superior response rates and survival for treatment‐naïve chronic lymphocytic leukemia (CLL) patients in a pivotal study that excluded patients younger than 65 (<65) and/or with chromosome 17p13 deletion (del(17p13)). We examined outcomes and toxicities of CLL patients who would have been excluded from the pivotal study, speci...
Article
Full-text available
Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A to...
Article
Full-text available
Clinical trials that led to ibrutinib's approval in chronic lymphocytic leukemia showed that its side effects differ from traditional chemotherapy toxicities. Reasons for discontinuation in clinical practice have not been adequately studied. We conducted a retrospective analysis of chronic lymphocytic leukemia patients treated with ibrutinib either...
Article
ONC201, founding member of the imipridone class of small molecules, is currently being evaluated in advancer cancer clinical trials. We explored single agent and combinatorial efficacy of ONC201 in preclinical models of hematological malignancies. ONC201 demonstrated (GI50 1–8 µM) dose- and time-dependent efficacy in acute myeloid leukemia (AML), a...
Article
Anti-PD-1 therapy is a novel immune-checkpoint inhibition therapy with tremendous potential in treating refractory/relapsed cancers. The 20year journey of human PD-1 research went through 3 phases: 1) discovering PD-1 gene structure and genomic organization, 2) understanding the mechanism of PD-1 mediated immune-checkpoint regulatory effects in coo...
Article
Previous studies have linked increased frequency of glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency with genomic instability and the risk of carcinogenesis. Recently, Phosphatidylinositol Glycan Anchor Biosynthesis; Class N (PIGN), a gene participating in GPI-AP synthesis, was suggested as a cancer chromosomal instability suppressor...
Article
TPS7569 Background: Although kinase inhibitor (KI) therapies, such as ibrutinib, are generally well tolerated, intolerance is the most common reason for discontinuation (d/c) in practice (~50%, Mato et al, Blood 2016). Additionally KI interruptions (≥ 8 days) can shorten OS (Barr et al, ASCO 2015). Fortunately, data suggest that KIs have non-overla...
Article
Full-text available
Primary myelofibrosis is a unique entity among BCR-ABL-negative myeloproliferative diseases, manifesting as bone marrow fibrosis and pancytopenia. Considerable evidence indicates that genetic and epigenetic abnormalities can result in defective clonal hematopoietic stem cell proliferation in addition to bone marrow microenvironment alteration. The...
Article
Full-text available
Previous studies have linked increased frequency of glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency with genomic instability and the risk of carcinogenesis. However, the underlying mechanism is still not clear. A randomForest analysis of the gene expression array data from 55 MDS patients (GSE4619) demonstrated a significant (p = 0....
Article
Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the US. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reas...
Article
Introduction: Ibrutinib (Ibr) is a kinase inhibitor (KI) indicated for treating CLL. Clinical trials that led to its approval showed that its unique side effects differ from traditional chemotherapy toxicities. We previously reported (Mato et al, ASH 2015) that intolerance was the most common reason for discontinuation of Ibr in 123 patients treate...
Article
Introduction: Ibrutinib (Ibr), idelalisib (Ide), andvenetoclax (Ven), are all now approved for treating CLL patients in the US. However, in the absence of head-to-head comparator trials, there is limited guidance as to the optimal sequence of these therapies and to the best choice upon failure of first selected agent. To address these gaps in curre...
Article
ONC201 is the founding member of the imipridone class of anti-cancer small molecules that possess a unique core chemical structure. ONC201 is currently being evaluated in several Phase I/II clinical trials for advanced cancers. In the current study, we evaluated the single agent and combinatorial efficacy of ONC201 in preclinical models of acute le...
Article
Background: Mantle cell lymphoma (MCL) is a moderately aggressive and incurable small to medium size B cell lymphoma. There is no standardized treatment for this disease. The conventional chemotherapy results in a high incidence of treatment related toxicity with frequent disease relapse. Cladribine is a hypomethylating agent that indirectly downre...
Article
Full-text available
B-cell receptor kinase inhibitor (KI) therapy represents a paradigm shift in chronic lymphocytic leukemia (CLL) management, but data on practice patterns after KI discontinuation and optimal sequencing are limited. We conducted a multicenter, retrospective, comprehensive analysis on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who disco...
Article
Introduction: B cell receptor signal transduction kinase inhibitors (KI) represent a paradigm shift in CLL management; however, there are limited data regarding real world practice patterns of KI discontinuation and response to subsequent therapies. Two centers reported outcomes of ibrutinib (Ibr) failure patients (pts) treated on clinical trials (...
Article
ONC201/TIC10 is a potent small molecule anti-tumor agent in several types of solid tumors and lymphomas. ONC201/TIC10 is on track to enter clinical trials for patients with advanced cancer in 2014, with IND issued by the FDA in March, 2014. Early trials will evaluate the safety and efficacy of ONC201/TIC10 as a monoagent in hematological malignanci...
Article
Background: Mantle cell lymphoma (MCL) is incurable with chemo-immunotherapy. Epigenetic modifications including altered DNA methylation and histone acetylation previously identified in MCL has provided the rationale for using the combination of a hypomethylating agent and a histone deactylase inhibitor. We aimed to study a combination of agents wi...
Article
PI3K/Akt and Ras/MAPK pathways are attractive therapeutic targets in almost all tumor types, including AML and MM. Apo2L/TRAIL has been deemed a promising therapeutic given its selectivity towards cancer cells although its clinical development has been hampered by various limitations including short half-life and general shortcoming of protein-base...
Article
The antitumor protein recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anticancer therapy although it has notable shortcomings that have limited its clinical development. Our lab previously identified a novel use for TRAIL-inducing compound 10 (ONC201/TIC10) as an efficacious antitumor therapeutic that indu...
Article
Quinacrine is a bioactive acridine derivative which has been used for treatment of malaria, giardiasis, systemic lupus erythematosus, and rheumatoid arthritis. In searching for p53 pathway activating agents for cancer therapy, we found that quinacrine stabilizes p53 and induces p53-dependent and p53-independent tumor cell death. Quinacrine also ind...
Article
Background: Umbilical cord blood (UCB) is rich in primitive hematopoietic stem cells (HSC) and progenitor cells that can reconstitute the hematopoietic system in recipients under proper conditioning. Initially umbilical cord blood transplantation was limited to children because of the low cell dose requirement. Both related and unrelated cord blood...
Conference Paper
ONC201/TIC10 is a potent small molecule anti-tumor agent in several types of solid tumors and lymphomas. ONC201/TIC10 is on track to enter clinical trials for patients with advanced cancer in 2014, with IND issued by the FDA in March, 2014. Early trials will evaluate the safety and efficacy of ONC201/TIC10 as a monoagent in hematological malignanci...
Article
Full-text available
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, clonal, hematopoietic stem cell disorder that manifests with a complement-mediated hemolytic anemia, bone marrow failure and a propensity for thrombosis. These patients experience both intra- and extravascular hemolysis in the context of underlying complement activation. Currently eculizumab effe...
Article
Dear Editor,Atypical hemolytic uremic syndrome (aHUS) is a life-threatening complement-mediated thrombotic microangiopathy that leads to progressive thrombocytopenia, kidney injury, mental status changes, and even death if without proper treatment [1]. Eculizumab is so far the only medication that effectively resolves the clinical symptoms and sign...
Article
Background Aplastic anemia (AA) and hypocellular myelodysplastic syndrome (MDS) are two common acquired bone marrow failure diseases. AA is mostly an acquired bone marrow disease caused by cellular and humoral mediated immune attack of hematopoietic stem cells (HSC) due to dysregulation of lymphocytic system, which leads to hematopoietic progenitor...
Article
7032 Background: PNH is a clonal disorder originating from a multipotent hematopoietic stem cell (HSC) acquiring a PIG-A gene mutation. PIG-A mutation lead to glycosylphosphatidylinositol-anchor protein (GPI-AP) deficiency, which contributes to many manifestations of PNH. About 25% of MDS and MPD, and 60% of AA also harbor small population of PNH-l...
Article
Patients with cytopenias and a cellular bone marrow can be a diagnostic and a therapeutic challenge. Previous reports have suggested a role for progenitor assays as a potentially useful test for diagnosis and predicting response to therapy. Here we report the results of BFU-E assays in 48 consultative cases of single or multi-lineage cytopenias wit...
Article
Full-text available
Patients with paroxysmal nocturnal hemoglobinuria harbor clonal glycosylphosphatidylinositol-anchor deficient cells arising from a multipotent hematopoietic stem cell acquiring a PIG-A mutation. Many patients with aplastic anemia and myelodysplastic syndromes also harbor small populations of glycosylphosphatidylinositol-anchor deficient cells. Pati...
Article
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease that presents with protean manifestations. Clinical and laboratory investigation over the past 25 years has uncovered most of the basic science underpinnings of PNH and has led to the development of a highly effective targeted therapy. PNH originates from a multipotent hematopo...
Article
Full-text available
Gallbladder carcinosarcoma is a rare gastrointestinal tract malignant tumour, which contains both epithelial cancer component and mesenchymal sarcoma component. Because of its unique anatomic location and unspecific medical presentation, preoperative diagnosis is difficult. The prognosis of gallbladder carcinoma is poor with median survival time of...
Article
 To investigate the natural history of paroxysmal nocturnal hemoglobinuria (PNH) clones in patients with acquired aplastic anemia (AA).  Twenty-seven patients with AA and a detectable PNH clone were monitored for a median of 5.7 years (range 1.5-11.5 years). Twenty-two patients received high-dose cyclophosphamide (HiCy) therapy. The erythrocyte and...
Article
4433 Introduction Aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplastic syndromes (MDS) are acquired bone marrow failure diseases. About 15% AA patients eventually transform to classical PNH; however, MDS patients almost never evolve to classical PNH. PNH originates from a multipotent HSC that acquires a PIG-A mutati...
Article
4428 Introduction Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are closely related bone marrow failure disorders. Most AA results from an autoimmune attack directed against hematopoietic stem/progenitor cells. PNH originates from a multipotent hematopoietic stem cell (HSC) that acquires a PIG-A mutation. The PIG-A ge...
Article
Full-text available
Very few human genes can be used to identify spontaneous inactivating somatic mutations. We hypothesized that because the XK gene is X-linked, it would be easy to identify spontaneously arising red cells with a phenotype resembling the McLeod syndrome, which results from inherited XK mutations. Here, by flow cytometry, we detect such phenotypic var...
Article
Most spontaneous somatic mutations in humans would be difficult to detect, because they are either silent or lethal, and for autosomal genes, there is a second functional copy that would complement the mutant phenotype. For the detection of spontaneous inactivating mutations, there is a great advantage to studying sentinel genes on the X-chromosome...
Article
IgD Multiple Myeloma accounts only for 2% of all Multiple Myeloma cases. It has been associated with various conditions and with complications involving many organs. The prognosis for IgD Multiple Myeloma is poor. This case report describes how a patient was diagnosed as IgD Lambda Multiple Myeloma complicated with left femoral head Amyloidosis. In...
Article
Kell and XK, two distinct red blood cell membrane proteins, are linked by a disulfide bond and form the Kell blood group complex. Kell surface antigens are expressed early during erythropoiesis but the onset of expression of XK which carries the Kx antigen is unknown. To determine whether Kell and XK are synchronously expressed, sorted human hemato...
Chapter
Kell is a 93kDa type II membrane glycoprotein that exists in over 25 different polymorphic forms and, because various forms are immunogenic, it is considered to be an important blood group protein. On red cells, Kell protein is linked by a single disulfide bond to another protein, XK that is lacking in the McLeod phenotype. Kell and XK are preferen...
Article
Erythropoietin (Epo) transduces mitogenic and chemoattractant signals to human endothelial cells. Identifications of Epo-responsive genes are important for understanding the molecular nature of Epo signaling in endothelial cells. The effects of Epo on differential expression of various genes were examined in human microvascular endothelial cells (H...