11,320 results match your criteria Leukemia[Journal]


Optimized induction of mitochondrial apoptosis for chemotherapy-free treatment of BCR-ABL+acute lymphoblastic leukemia.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.

BCR-ABL+acute lymphoblastic leukemia (ALL) in adults has a poor prognosis with allogeneic stem cell transplantation (SCT) considered the best curative option for suitable patients. We here characterize the curative potential of BH3-mimetics differentially targeting mitochondrial BCL2-family members using a combination therapy approach with dexamethasone and tyrosine kinase inhibitors targeting BCR-ABL. In BCR-ABL + ALL BH3-mimetics act by redistribution of mitochondrial activator BIM, which is strongly required for cytotoxicity of the BCL2-specific BH3-mimetic ABT-199, tyrosine kinase inhibitors (TKIs) and dexamethasone. Read More

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December 2018

Epidemiology of bloodstream infections in patients with chronic lymphocytic leukemia: a longitudinal nation-wide cohort study.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Department of Haematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Patients with chronic lymphocytic leukemia (CLL) have a high risk of bloodstream infections (BSI). BSI cause significant morbidity and mortality among CLL patients; approximately one-third of fatalities in CLL list infections as cause of death. All CLL patients in Denmark diagnosed between 2008 and 2016 were followed through registries for the event of a BSI. Read More

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December 2018

Global long terminal repeat activation participates in establishing the unique gene expression programme of classical Hodgkin lymphoma.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Institute for Cancer and Genomic Sciences, University of Birmingham, College of Medical and Dental Sciences, Birmingham, B152TT, UK.

Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported in classical Hodgkin Lymphoma (cHL) that a member of the THE1B class of LTR elements acted as a promoter for the proto-oncogene and growth factor receptor gene CSF1R and that expression of this gene is required for cHL tumour survival. Read More

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December 2018

Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma.

Leukemia 2018 Dec 13. Epub 2018 Dec 13.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Extranodal natural killer T-cell lymphoma (nasal type; NKTCL) is an aggressive malignancy strongly associated with Epstein-Barr virus (EBV) infection. However, the role of EBV in NKTCL development is unclear, largely due to the lack of information about EBV genome and transcriptome in NKTCL. Here, using high-throughput sequencing, we obtained whole genome (n = 27) and transcriptome datasets (n = 18) of EBV derived from NKTCL tumor biopsies. Read More

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December 2018

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis.

Leukemia 2018 Dec 12. Epub 2018 Dec 12.

Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, CIBERONC Pamplona, Pamplona, Spain.

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). Read More

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December 2018

CD34CD38 leukemic stem cell frequency to predict outcome in acute myeloid leukemia.

Leukemia 2018 Dec 12. Epub 2018 Dec 12.

Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.

Current risk algorithms are primarily based on pre-treatment factors and imperfectly predict outcome in acute myeloid leukemia (AML). We introduce and validate a post-treatment approach of leukemic stem cell (LSC) assessment for prediction of outcome. LSC containing CD34+CD38- fractions were measured using flow cytometry in an add-on study of the HOVON102/SAKK trial. Read More

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December 2018

Blood and skin-derived Sezary cells: differences in proliferation-index, activation of PI3K/AKT/mTORC1 pathway and its prognostic relevance.

Leukemia 2018 Dec 5. Epub 2018 Dec 5.

Istituto Dermopatico dell'Immacolata, IDI-IRCCS, 00167, Rome, Italy.

Sézary syndrome (SS) is a rare and aggressive variant of Cutaneous T-Cell Lymphoma characterized by neoplastic distribution mainly involving blood, skin, and lymph-node. Although a role of the skin microenvironment in SS pathogenesis has long been hypothesized, its function in vivo is poorly characterized. To deepen this aspect, here we compared skin to blood-derived SS cells concurrently obtained from SS patients highlighting a greater proliferation-index and a PI3K/AKT/mTORC1 pathway activation level, particularly of mTOR protein, in skin-derived-SS cells. Read More

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December 2018
2 Reads

Depletion of Ars2 inhibits cell proliferation and leukemogenesis in acute myeloid leukemia by modulating the miR-6734-3p/p27 axis.

Leukemia 2018 Dec 5. Epub 2018 Dec 5.

College of Pharmacy, Army Medical University, Chongqing, China.

Ars2 is a component of the nuclear cap-binding complex (CBC) that contributes to microRNA biogenesis and is required for cellular proliferation. Little is known regarding the functional role of Ars2 in cell proliferation and leukemogenesis of acute myeloid leukemia. Here, we show that the elevated expression of Ars2 was observed in acute myeloid leukemia (AML) cell lines and bone marrow samples from AML patients and was correlated with poorer overall survival. Read More

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December 2018
2 Reads

Indications and use of therapeutic phlebotomy in polycythemia vera: which role for erythrocytapheresis?

Leukemia 2018 Dec 5. Epub 2018 Dec 5.

Fondazione Policlinico Universitario A. Gemelli IRCCS and Istituto di Ematologia, Università Cattolica, Roma, Italy.

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December 2018
1 Read

Single-cell analysis identifies CRLF2 rearrangements as both early and late events in Down syndrome and non-Down syndrome acute lymphoblastic leukaemia.

Leukemia 2018 Nov 28. Epub 2018 Nov 28.

Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK.

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5-15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We have previously reported the genomic landscape of patients with CRLF2 rearrangements (CRLF2-r) using both whole genome and exome sequencing, which identified a number of potential clonal and sub-clonal genomic alterations. In this study, we aimed to assess when the CRLF2-r; IGH-CRLF2 or P2RY8-CRLF2, arose during the evolution of both Down syndrome-ALL (DS-ALL) and non-DS-ALL. Read More

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November 2018

JAK2V617F but not CALR mutations confer increased molecular responses to interferon-α via JAK1/STAT1 activation.

Leukemia 2018 Nov 23. Epub 2018 Nov 23.

Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

Pegylated interferon-α (peg-IFNa) treatment induces molecular responses (MR) in patients with myeloproliferative neoplasms (MPNs), including partial MR (PMR) in 30-40% of patients. Here, we compared the efficacy of IFNa treatment in JAK2V617F- vs. calreticulin (CALR)-mutated cells and investigated the mechanisms of differential response. Read More

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November 2018
4 Reads

MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells.

Leukemia 2018 Nov 23. Epub 2018 Nov 23.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.

Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. T(4;14) MM overexpresses multiple myeloma SET domain-containing protein (MMSET). MMSET has three major isoforms: the full-length form MMSET II and the short isoforms REIIBP and MMSET I. Read More

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November 2018
4 Reads

Combination treatment of acute myeloid leukemia cells with DNMT and HDAC inhibitors: predominant synergistic gene downregulation associated with gene body demethylation.

Leukemia 2018 Nov 23. Epub 2018 Nov 23.

Division of Hematology, Oncology and Stem Cell Transplantation, Department of Internal Medicine, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

DNA methyltransferase inhibitors (DNMTi) approved for older AML patients are clinically tested in combination with histone deacetylase inhibitors (HDACi). The mechanism of action of these drugs is still under debate. In colon cancer cells, 5-aza-2'-deoxycytidine (DAC) can downregulate oncogenes and metabolic genes by reversing gene body DNA methylation, thus implicating gene body methylation as a novel drug target. Read More

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November 2018
4 Reads

Creatine kinase pathway inhibition alters GSK3 and WNT signaling in EVI1-positive AML.

Leukemia 2018 Nov 2. Epub 2018 Nov 2.

INSERM UMR 944, Institut Universitaire d'Hématologie, Hôpital St. Louis, Paris, France.

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November 2018
10.431 Impact Factor

Cancer from the perspective of stem cells and misappropriated tissue regeneration mechanisms.

Leukemia 2018 Dec 30;32(12):2519-2526. Epub 2018 Oct 30.

Stem Cell Institute, Division of Hematology and Oncology, James Graham Brown Cancer Center, University Louisville, 500 South Floyd Street, Louisville, 40202, Kentucky, USA.

Tumorigenesis can be considered as pathologically misappropriated tissue regeneration. In this review we will address some unresolved issues that support this concept. First, we will address the issue of the identity of cancer-initiating cells and the presence of cancer stem cells in growing tumors. Read More

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December 2018
1 Read

Targeted killing of TNFR2-expressing tumor cells and T by TNFR2 antagonistic antibodies in advanced Sézary syndrome.

Leukemia 2018 Oct 24. Epub 2018 Oct 24.

Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Rm 3602, 02129, Boston, MA, USA.

Sézary syndrome (SS) is a rare form of cutaneous T-cell lymphoma often refractory to treatment. SS is defined as adenopathy, erythroderma with high numbers of atypical T cells. This offers an opportunity for new interventions and perhaps antibody-based therapeutic by virtue of its high expression of the TNFR2 oncogene on the tumor cells and on T-regulatory cells (T). Read More

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October 2018
15 Reads

IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective γ-chain cytokines, decreases leukemic T-cell viability.

Leukemia 2018 Oct 23. Epub 2018 Oct 23.

University of Virginia Cancer Center and Department of Medicine, Division of Hematology & Oncology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.

Interleukin-15 (IL-15) and IL-2 drive T-cell malignancies including T-cell large granular lymphocyte leukemia (T-LGLL) and HTLV-1 driven adult T-cell leukemia (ATL). Both cytokines share common γ-chain receptors and downstream signaling pathways. T-LGLL is characterized by clonal expansion of cytotoxic T cells and is associated with abnormal JAK/STAT signaling. Read More

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October 2018
2 Reads

De novo gene mutations in normal human memory B cells.

Leukemia 2018 Oct 23. Epub 2018 Oct 23.

Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.

In the past years, the genomes of thousands of tumors have been elucidated. To date however, our knowledge on somatic gene alterations in normal cells is very limited. In this study, we demonstrate that tetanus-specific human memory B lymphocytes carry a substantial number of somatic mutations in the coding regions of the genome. Read More

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October 2018

Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL.

Leukemia 2018 Oct 23. Epub 2018 Oct 23.

Department of Molecular Medicine, University of Padua, Padua, Italy.

Protein phosphatase 2 A (PP2A) is a tumour suppressor whose strong inhibition underlies the phosphorylation-dependent, anti-apoptotic mechanisms in Chronic Lymphocytic Leukemia (CLL). Inactivation of PP2A is due to the cooperative action of the phosphorylation of Y307 of its catalytic subunit by the aberrant cytosolic pool of the Src Family Kinase Lyn and the interaction with its protein inhibitor SET, which is overexpressed in CLL. In this study, we developed a library of compounds, the most potent being the one named CC11, which restores PP2A activity by disrupting the PP2A/SET complex, thereby triggering the mitochondrial pathway of apoptosis. Read More

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October 2018
1 Read

Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse.

Leukemia 2018 Oct 15. Epub 2018 Oct 15.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Achieving a complete response (CR) is associated with improved overall survival (OS) in multiple myeloma (MM), but data on duration of CR (DurCR) are limited. We evaluated 351 patients (2004-2016), achieving CR with first-line therapy. Patients with sustained DurCR ≥ 24 months (n = 177) had better OS; 150 vs. Read More

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October 2018
6 Reads

SMC3 protein levels impact on karyotype and outcome in acute myeloid leukemia.

Leukemia 2018 Oct 15. Epub 2018 Oct 15.

Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.

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October 2018
2 Reads

Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

Leukemia 2018 Oct 12. Epub 2018 Oct 12.

Mayo Clinic Cancer Center, Jacksonville, FL, USA.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34. Read More

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October 2018
5 Reads

CAR T-cells for T-cell malignancies: challenges in distinguishing between therapeutic, normal, and neoplastic T-cells.

Leukemia 2018 Nov 12;32(11):2307-2315. Epub 2018 Oct 12.

CHU Rennes, Service Hématologie Clinique, 35033, Rennes, France.

Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrated remarkable efficacy for the treatment of B-cell malignancies. The development of CAR T-cells against T-cell malignancies appears more challenging due to the similarities between the therapeutic, normal and malignant T-cells. The obstacles include CAR T-cell fratricide, T-cell aplasia, and contamination of CAR T-cell products with malignant T-cells. Read More

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November 2018
1 Read

Relative survival following response to 7 + 3 versus azacytidine is similar in acute myeloid leukemia and high-risk myelodysplastic syndromes: an analysis of four SWOG studies.

Leukemia 2018 Oct 12. Epub 2018 Oct 12.

Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Here we quantify and compare the absolute and relative overall survival (OS) benefits conveyed by complete remission (CR) in AML and high-risk MDS, and by CR with incomplete count recovery (CRi) in AML and by hematologic improvement (HI) in MDS, following treatment with 7 + 3 versus azacytidine. We compared patients receiving 7 + 3 in SWOG studies S0106 (n = 301) and S1203 (n = 261) enrolling adults ≤ 60 years, with patients receiving azacytidine therapies in S0703 (n = 133 AML patients ≥ 60) and S1117 (n = 277 MDS patients ≥ 18). Absolute survival benefit was evaluated with 1-year, 3-year, and median OS; relative benefit was evaluated with univariate and covariate-adjusted hazard ratios. Read More

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October 2018
2 Reads

Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells.

Leukemia 2018 Dec 12;32(12):2572-2579. Epub 2018 Oct 12.

Cancer Theme, South Australian Health & Medical Research Institute, Adelaide, Australia.

Following the achievement of deep molecular response on tyrosine kinase inhibitors (TKIs), approximately half of patients with chronic myeloid leukemia (CML) can discontinue TKI and remain in treatment-free remission (TFR). The ALLG CML8 study enrolled 40 imatinib-treated patients with undetectable BCR-ABL1 mRNA (approximately MR). Molecular relapse was defined as detectable BCR-ABL1 on two consecutive tests or any single value >0. Read More

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December 2018
2 Reads
10.431 Impact Factor

DUX4-DNA structure reveals new insight into DUX4-Responsive-Element.

Leukemia 2018 Oct 12. Epub 2018 Oct 12.

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai JiaoTong University School of Medicine and School of Life Sciences and Biotechnology, Shanghai JiaoTong University, 197 Ruijin Er Road, Shanghai, 200025, China.

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October 2018

Inhibitors of the protein disulfide isomerase family for the treatment of multiple myeloma.

Leukemia 2018 Oct 12. Epub 2018 Oct 12.

Department of Cell and Molecular Pharmacology & Experimental Therapeutics, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.

Multiple Myeloma (MM) is highly sensitive to disruptions in cellular protein homeostasis. Proteasome inhibitors (PIs) are initially effective in the treatment of MM, although cures are not achievable and the emergence of resistance limits the durability of responses. New therapies are needed for refractory patients, and those that combat resistance to standard of care agents would be particularly valuable. Read More

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October 2018
2 Reads

Bone marrow hematopoietic dysfunction in untreated chronic lymphocytic leukemia patients.

Leukemia 2018 Oct 5. Epub 2018 Oct 5.

Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA.

The consequences of immune dysfunction in B-chronic lymphocytic leukemia (CLL) likely relate to the incidence of serious recurrent infections and second malignancies that plague CLL patients. The well-described immune abnormalities are not able to consistently explain these complications. Here, we report bone marrow (BM) hematopoietic dysfunction in early and late stage untreated CLL patients. Read More

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October 2018
2 Reads

Histone deacetylase inhibitor targets CD123/CD47-positive cells and reverse chemoresistance phenotype in acute myeloid leukemia.

Leukemia 2018 Oct 5. Epub 2018 Oct 5.

Department of Anatomy and Cell Biology; College of Medicine, UF Health Cancer Center, University of Florida, Gainesville, FL, USA.

Chemoresistance may be due to the survival of leukemia stem cells (LSCs) that are quiescent and not responsive to chemotherapy or lie on the intrinsic or acquired resistance of the specific pool of AML cells. Here, we found, among well-established LSC markers, only CD123 and CD47 are correlated with AML cell chemosensitivities across cell lines and patient samples. Further study reveals that percentages of CD123CD47 cells significantly increased in chemoresistant lines compared to parental cell lines. Read More

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October 2018
2 Reads

Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study.

Leukemia 2018 Dec 1;32(12):2558-2571. Epub 2018 Oct 1.

Department of Medicine III, University Hospital LMU Campus Grosshadern, Munich, Germany.

Dose-dense induction with the S-HAM regimen was compared to standard double induction therapy in adult patients with newly diagnosed acute myeloid leukemia. Patients were centrally randomized (1:1) between S-HAM (2nd chemotherapy cycle starting on day 8 = "dose-dense") and double induction with TAD-HAM or HAM(-HAM) (2nd cycle starting on day 21 = "standard"). 387 evaluable patients were randomly assigned to S-HAM (N = 203) and to standard double induction (N = 184). Read More

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December 2018
9 Reads
10.431 Impact Factor

Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure.

Leukemia 2018 Oct 1. Epub 2018 Oct 1.

Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.

Cancer-causing genome instability is a major concern during space travel due to exposure of astronauts to potent sources of high-linear energy transfer (LET) ionizing radiation. Hematopoietic stem cells (HSCs) are particularly susceptible to genotoxic stress, and accumulation of damage can lead to HSC dysfunction and oncogenesis. Our group recently demonstrated that aging human HSCs accumulate microsatellite instability coincident with loss of MLH1, a DNA Mismatch Repair (MMR) protein, which could reasonably predispose to radiation-induced HSC malignancies. Read More

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October 2018
2 Reads

Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care.

Leukemia 2018 Dec 1;32(12):2546-2557. Epub 2018 Oct 1.

Hôpital Saint Louis, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, France.

Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. Read More

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December 2018
10 Reads

The NF1 hotspot in acute myeloid leukemia: what's in a name?

Leukemia 2018 Dec 1;32(12):2715. Epub 2018 Oct 1.

Laboratory for Molecular Hematology, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.

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December 2018

Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia.

Leukemia 2018 Sep 28. Epub 2018 Sep 28.

Childrens Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, USA.

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. Read More

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September 2018
2 Reads

Control of chronic lymphocytic leukemia development by clonally-expanded CD8 T-cells that undergo functional exhaustion in secondary lymphoid tissues.

Leukemia 2018 Sep 28. Epub 2018 Sep 28.

Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Chronic lymphocytic leukemia (CLL) is associated with substantial alterations in T-cell composition and function. However, the role of T-cells in CLL remains largely controversial. Here, we utilized the Eµ-TCL1 mouse model of CLL as well as blood and lymph node samples of CLL patients to investigate the existence of anti-tumoral immune responses in CLL, and to characterize involved immune cell populations. Read More

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September 2018
1 Read

Exome sequencing of the TCL1 mouse model for CLL reveals genetic heterogeneity and dynamics during disease development.

Leukemia 2018 Sep 27. Epub 2018 Sep 27.

Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria.

The TCL1 mouse model is widely used to study pathophysiology, clonal evolution, and drug sensitivity or resistance of chronic lymphocytic leukemia (CLL). By performing whole exome sequencing, we present the genetic landscape of primary tumors from TCL1 mice and of TCL1 tumors serially transplanted into wild-type recipients to mimic clonal evolution. We show that similar to CLL patients, mutations in mice are frequently subclonal and heterogenous among different primary TCL1 mice. Read More

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September 2018
4 Reads