University of Wisconsin Hematology

White blood cells: function/pathology

  1. Margraf et al. Neutrophils in acute inflammation: current concepts and translational implications. Blood 2022;139:2130
  2. Silvestre-Roig et al. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood 2016;127:2173
  3. Wirths et al. Neutrophil homeostasis and its regulation by danger signaling. Blood 2014;123: 3563
  4. Castanheira and Kubes. Neutrophils and NETs in modulating acute and chronic inflammation. Blood 2019;133:2178
  5. Yipp and Kubes. NETosis: how vital is it? Blood 2013;122:2784 (Neutrophil extracellular traps)
  6. Martinod and Wagner. Thrombosis: tangled up in NETs. Blood 2014;123:2768(Role of neutrophils in thrombosis)
  7. Jorch and Kubes. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med 2017;23:279
  8. Pillay et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood 2010;116:625
  9. Craig et al. An upper bound for the half-removal time of neutrophils from circulation (letter). Blood 2016;128:1989(Less than 15 hours)
  10. Nolte and Margadant. Activation and suppression of hematopoietic integrins in hemostasis and immunity. Blood 2020;135:7
  11. Swirski and Nahrendorf. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 2013;339:161
  12. Geng et al. Emergence, origin, and function of neutrophil–dendritic cell hybrids in experimentally induced inflammatory lesions in mice. Blood 2013;121:1690(PMNs recruited into tissues can differentiate into PMN-DC hybrid cells)
  13. Gibson and Berliner. How we evaluate and treat neutropenia in adults. Blood 2014;124:1251
  14. Zon And Berliner. How I manage inpatient consultations for quantitative neutrophil abnormalities in adults. Blood 2023;142:786
  15. Bartels et al. Understanding chronic neutropenia: life is short. Br J Haematol 2016;172:157
  16. Hsieh et al. Prevalence of Neutropenia in the U.S. Population: Age, Sex, Smoking Status, and Ethnic Differences. Ann Intern Med 2007;146:486
  17. Nalls et al. Admixture Mapping of White Cell Count: Genetic Locus Responsible for Lower White Blood Cell Count in the Health ABC and Jackson Heart Studies. Am J Hum Genet 2008;82:81
  18. Legge et al. The Duffy-null genotype and risk of infection.  Hum Mol Genet 2020;29:3341 (Benign “ethnic” neutropenia)
  19. Papadaki et al. Impaired granulocytopoiesis in patients with chronic idiopathic neutropenia is associated with increased apoptosis of bone marrow myeloid progenitor cells. Blood 2003;101:2591
  20. Tsaknakis et al. Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia. Blood 2021;138:1249 (Prevalence <3%, 31-fold higher risk of transformation to myeloid neoplasm)
  21. Fioredda et al. Late-onset and long-lasting neutropenias in the young: A new entity anticipating immune-dysregulation disorders. Am J Hematol 2024;99:534
  22. Klein. C. Congenital neutropenia. Hematology 2009;344
  23. Newburger PE. Disorders of Neutrophil Number and Function. Hematology 2006;104-110
  24. Dinauer MC. Inflammatory consequences of inherited disorders affecting neutrophil function. Blood 2019;133:2130
  25. Dale et al. Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia (letter). NEJM 2017;377:2290 (Treatment is safe and effective)
  26. Horwitz et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 2007;109:1817
  27. de Fontbrune et al. Severe chronic primary neutropenia in adults: report on a series of 108 patients. Blood 2015;126:1643(Generally a benign entity. GCSF increases ANC but usually not needed. ANC <200 at diagnosis associated with higher rate of bacterial infxn)
  28. Zeidler et al. Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry. Haematologica 2014;99:1395
  29. Bellanné-Chantelot et al. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-Diamond–like syndrome. Blood 2018;132:1318
  30. Ibáñez et al. Population-Based Drug-Induced Agranulocytosis. Arch Intern Med 2005;165:869
  31. Andersohn et al. Systematic Review: Agranulocytosis Induced by Nonchemotherapy Drugs. Ann Intern Med 2007;146:657
  32. Levine et al. Neutropenia in Human Immunodeficiency Virus Infection. Data From the Women’s Interagency HIV Study. Arch Intern Med 2006;166:405
  33. Rosenberg et al. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 2006;107:4628
  34. Collin et al. Haematopoietic and immune defects associated with GATA2 mutation. Br J Haematol 2015;169:173
  35. Vinh et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 2010;115:1519
  36. Dickinson et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 2011;118:2656(myclobacterial infection, pulmonary alveolar proteinosis, MDS and AML)
  37. Hsu et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011;118:2653
  38. Pasquet et al. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood 2013;121:822
  39. Jacobsen et al. The expanding role(s) of eosinophils in health and disease. Blood 2012;120:3882
  40. Farahi et al. Use of 111-Indium–labeled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects. Blood 2012;120:4068
  41. Rothenbert M. Eosinophilia. NEJM 1998;338:1592
  42. Lombardi and Passalacqua. Eosinophilia and Diseases: Clinical Revision of 1862 Cases. Arch Intern Med 2003;163:1371
  43. Kuang FL. Approach to the patient with eosinophilia. Med Clin NA 2020;104:1
  44. Klion AD. Approach to the patient with suspected hypereosinophilic syndrome. Hematology Am Soc Hematol Educ Program 2022: 47
  45. Phipps et al. Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007;110:1578
  46. Kroshinsky et al. Drug Reaction with Eosinophilia and Systemic Symptoms. NEJM 2024;391:2242
  47. Metcalfe D. Mast cells and mastocytosis. Blood 2008;112:946
  48. Pejler et al. Mast cell proteases: multifaceted regulators of inflammatory disease. Blood 2010;115:4981
  49. Kunder et al. Mast cell modulation of the vascular and lymphatic endothelium. Blood 2011;118:5383
  50. Dale et al. The phagocytes: neutrophils and monocytes. Blood 2008;112:935
  51. Zhu and Paul CD4 T cells: fates, functions, and faults. Blood 2008;112:1557
  52. LeBien and Tedder. B lymphocytes: how the develop and function. Blood 2008;112:1570
  53. Caligiuri M. Human natural killer cells. Blood 2008;112:461
  54. Natkunam Y. The biology of the germinal center. Hematology 2007:210
  55. Gansner et al. Plateletpheresis-associated lymphopenia in frequent platelet donors. Blood 2019;133;605

Biology of cancer

  1. Siegel et al. Cancer statistics, 2015. CA 2015;65: 5
  2. Fröhling and Döhner. Chromosomal abnormalities in cancer. NEJM 2008;359:722
  3. Croce C. Oncogenes and cancer. NEJM 2008;358:502
  4. Uhlen et al. A pathology atlas of the human cancer transcriptome. Science 2017;357:eaan2507
  5. Dawson MA. The cancer epigenome: Concepts, challenges, and therapeutic opportunities. Science 2017;355:1147
  6. Huff et al. The paradox of response and survival in cancer therapeutics. Blood 2006;107:431(Cancer stem cells)
  7. Vogelstein et al. Cancer genome landscapes. Science 2013;339:1546
  8. Hahn and Weinberg. Rules for making human tumor cells. NEJM 2002;347:1593
  9. Hotchkiss et al. Mechanisms of disease: cell death. NEJM 2009;1570
  10. Palucka and Coussens. The basis of oncoimmunology. Cell 2016;164:1233
  11. Boussiotis VA. Molecular and biochemical aspects of the PD-1 checkpoint pathway. NEJM 2016;375:1767
  12. Binnewies et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 2018;24:541
  13. Tomasetti and Vogelstein. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2015;347:78(Oncogenic mutations happen in proportion to the number of dividing stem cells in a tissue; with editorial)
  14. Popovic et al. Ubiquitination in disease pathogenesis and treatment. Nat Med 2014;20:1242
  15. Esteller M. Epigenetics in cancer. NEJM 2008;358:1148
  16. Aparicio and Caldas. The implications of clonal genome evolution for cancer medicine. NEJM 2013;368:842
  17. Yue and Rao.TET family dioxygenases and the TET activator vitamin C in immune responses and cancer. Blood 2020;136:1394
  18. Roodman GD.  Mechanisms of bone metastasis.  NEJM 2004;350:1655
  19. Chiang and Massagué. Molecular basis of metastasis. NEJM 2008;359:2814
  20. Leong and Karsan. Recent insights into the role of Notch signaling in tumorigenesis. Blood 2006;107:2223
  21. Platanias L.  MAP kinase signalling pathways and hematologic malignancies.  Blood 2003;101:4667
  22. Chen et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature 2016;535:148
  23. Murtaza et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 2013;497:108
  24. Andor et al. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nat Med 2016;22:105
  25. Casey et al. The MYC oncogene is a global regulator of the immune response. Blood 2018;131:2007(“MYC may…prevent highly proliferative cells from eliciting an immune response. MYC-induced tumors may be particularly sensitive to immuno-oncology therapeutic interventions”)
  26. Xu et al. Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents. Blood 2018;131:1777
  27. Gordon-Alonso et al. Extracellular galectins as controllers of cytokines in hematological cancer. Blood 2018;132:484
  28. Reiter et al. Minimal functional driver gene heterogeneity among untreated metastases. Science 2018;361:6406(A single biopsy provides adequate information about driver genes in metastatic disease)
  29. Helmink et al. The microbiome, cancer, and cancer therapy. Nat Med 2019;25:377

CHIP & CCUS

  1. Boettcher and Ebert. Clonal hematopoiesis of indeterminate potential. J Clin Oncol 2019;37:419
  2. Challen and Goodell. Clonal hematopoiesis: mechanisms driving dominance of stem cell clones. Blood 2020;136:1590
  3. Warren and Link. Clonal hematopoiesis and risk for hematologic malignancy. Blood 2020;136:1599
  4. Jaiswal S. Clonal hematopoiesis and nonhematologic disorders. Blood 2020;136:1606
  5. Shlush LI. Age-related clonal hematopoiesis. Blood 2018;131:496
  6. Jaiswal et al. Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. NEJM 2014:371:2488(>10 fold increased risk of heme malignancy in pts with somatic mutations in peripheral blood cells)
  7. Xie et al.Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014;20:1472(“The blood cells of more than 2% of individuals [5–6% of people older than 70 years] contain mutations that may represent premalignant events)
  8. Rossi et al. Clinical relevance of clonal hematopoiesis in persons aged ≥80 years. Blood 2021;138:2093 (Specific mutational patterns predict risk of evolution to myeloid neoplasia)
  9. Watson et al. The evolutionary dynamics and fitness landscape of clonal hematopoiesis. Science 2020;367:6485
  10. Genovese et al. Clonal Hematopoiesis and Blood-Cancer Risk Inferred from Blood DNA Sequence. NEJM 2014;371:2477(Results similar to above article)
  11. Steensma et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 2015;126:9
  12. Steensma D. Predicting therapy-related myeloid neoplasms – and preventing them? Lancet Oncol 2017;18:11(Overt malignancy develops at a rate of 0.5-1% per year in people with CHIP)
  13. Jaiswal et al. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. NEJM 2017;377:111(CHIP associated with 2x higher risk of CAD in humans and accelerated atherosclerosis in mouse model)
  14. Libby abd Ebert. CHIP (Clonal Hematopoiesis of Indeterminate Potential). Potent and Newly Recognized Contributor to Cardiovascular Risk. Circulation 2018;138:666
  15. Miller et al. Association of clonal hematopoiesis with chronic obstructive pulmonary disease. Blood 2022;139:357
  16. Agrawal et al. TET2-mutant clonal hematopoiesis and risk of gout. Blood 2022;140:1094
  17. Zink et al. Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood 2017;130:742 (Evidence of clonal hematopoiesis found in less than 1% of those under 35 and over 50% in those over 85)
  18. Buscarlet et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 2017;130:753(TET2 mutations age-dependent, associated with mild neutropenia, showed some familial clustering)
  19. Malcovati et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood 2017;129:3371(Presence of somatic mutation increased likelihood of developing a myeloid neoplasm by about 14-fold)
  20. van Zeventer et al. Mutational spectrum and dynamics of clonal hematopoiesis in anemia of older individuals. Blood 2020;135:1161
  21. Cooper and Young. Clonality in context: hematopoietic clones in their marrow environment. Blood 2017;130:2363
  22. Nagase et al. Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation. J Exp Med 2018;215:1729(Mouse model of CHIP; see this discussion in NEJM)
  23. Meisel et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature 2018;557:580
  24. Desai et al. Somatic mutations precede acute myeloid leukemia years before diagnosis. Nat Med 2018;24:1015(IDH1, IDH2, TP53, DNMT3A, TET2 and spliceosome gene mutations predict progression to AML; with editorial)
  25. Loh et al. Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations. Nature 2018;559:350(Identifies several genetic loci that substantially increase risk to develop CHIP)
  26. Hansen et al. Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality. Blood 2020;135:261(No evidence that there is a genetic predisposition to CHIP or that it increases mortality)
  27. Fabre et al. Concordance for clonal hematopoiesis is limited in elderly twins. Blood 2020;135:269
  28. Bick et al Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 2020;586:763
  29. Tsaknakis et al. Incidence and prognosis of clonal hematopoiesis in patients with chronic idiopathic neutropenia. Blood 2021;138:1249 (Prevalence <3%, 31-fold higher risk of transformation to myeloid neoplasm)
  30. Galli et al. Relationship between clone metrics and clinical outcome in clonal cytopenia. Blood 2021;138:965 (30% of patients with idiopathic cytopenia have CCUS)

VEXAS syndrome

  1. Beck et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. NEJM 2020;383:2628(X-linked disorder; somatic hematopoietic stem cell mutations impair ubiquitination and protein degradation in phagocytes, activate autoimmune pathways)
  2. Arlet et al. Mutant UBA1 and Severe Adult-Onset Autoinflammatory Disease. NEJM 2021;384:2163(VEXAS syndrome in 2 women with acquired monosomy X)
  3. Grayson et al. VEXAS syndrome. Blood 2021;137:3591
  4. Bourbon et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021;137:3682
  5. Gurnari et al. Vacuolization of hematopoietic precursors: an enigma with multiple etiologies. Blood 2021;137:3685
  6. Ferrada et al. Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesisBlood 2022;140:1496