Director: Jaroslaw P. Maciejewski MD PhD
Laboratory manager and Study Coordinator: Susan Sunkle
Clinical data entry: Veronica Spprigs
Research Nurse: Robin Heggeland
Hematology clinical fellow: Abdo Haddad MD
Staff: 3 technicians, 6 Postodoctoral Fellows, 1 Medical Student, 3 Residents
The main goal of our section is to achieve integration between clinical care and research and laboratory investigations to improve diagnosis and therapy of hematologic disorders, including bone marrow failure syndromes and leukemia. Our studies and clinical trials target several hematologic disease and address various aspects including therapy, diagnosis and pathogenesis. Cancer Center Flow Cytometry Core. The laboratory is closely associated with the Clinical Program in Bone Marrow Failure Syndromes including:
- Aplastic Anemia (AA)
- Myelodysplastic Syndromes (MDS)
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Large Granular lymphocyte Leukemia (LGL)
- Single-lineage cytopenias: pure red cell aplasia (PRCA), and autoimmune neutropenia (AIN).
- Myeloproliferative syndromes (MPS).
Both clinical and laboratory programs are nationally and internationally renewed. We are a tertiary, referral center for bone marrow failure syndrome recommended by Aplastic Anemia and Myelodysplastic Syndrome International Foundation and receiuve designation "Center for excellence" of the Myelodysplastic Sundrome Foundation. Our clinical cancer research program is a part of NIH-funded Bone Marrow Failure Consortium. The laboratory research is funded by NIH grants, charitable donations of our patients and grants from Aplastic Anemia and Myelodysplastic Syndrome International Foundation. We maintain a clinical and laboratory training program in bone marrow failure syndromes funded through NIH U54 and K24 mechanisms.
The current laboratory research topics include 3 major areas:
- Immunobiology of bone marrow failure syndromes and graft versus hoist disease
- Gene chip analysis of genetic predisposition and acquired chromosomal changes in hematologic disease.
- Analysis of stem cell function in bone marrow failure syndromes
Specific research subjects are:
- Molecular analysis of T cell repertoire in AA, MDS and LGL to identify determinants of the stem cell specificity of autoimmune/leukemia-specific T cells.
- High density SNP array analysis of genetic variants associated with AA, PNH, MDS.
- Diagnostic application of SNP arrays and A-CGH to study chromosomal damage in MDS. Investigation of the defects in the DNA repair gene machinery.
- Study of stem cell dysfunction in age
- Defects in the stem cell function and immune recognition in PNH
- Molecular analysis of T cell repertoire in GvHD.
- Identification of molecular lesions in MDS and MPD/MPS including Jak2 mutations
- Study of the pathophysiologic mechanisms in LGL leukemia and other clonal T cell disorders.
- Basic molecular biology of T cell receptor and construction of soluble T cells receptor
Our most recent publications include:
1. Young NS, Maciejewski JP, Sloand E, Zeng W, Chen G, Risitano AM, Myiazato A (2002) The relationship of aplastic anemia and PNH. Int. J. Hematol. 76, 168-172
2. Maciejewski JP, Risitano A, Kook H, Zeng Z, Chen G, Young NS (2002) Immune pathophysiology of aplastic anemia. Int. J. Hematol. 76, 207-214
3. Plasilova M, Risitano A, Maciejewski JP. (2003) Application of the molecular analysis of the T-cell receptor repertoire in the study of immune-mediated hematologic diseases. Hematology 8:173-181.
4. Maciejewski JP and Selleri C. (2003). Evolution of clonal cytogenetic abnormalities in aplastic anemia. Leukemia Lymphoma, 45:433-440
5. Maciejewski JP and Risitano AM. (2003). Hematopoietic stem cells in Aplastic Anemia. Arch. Med. Res. 34:528-544
6. Chen G, Kook H, Zeng W, Young NS and Maciejewski JP. (2003). Is there a direct effect of antithymocyte globulin on hematopoiesis? J. Hematol 5:255-261.
7. O'Keefe C, Maciejewski JP, Risitano AM (2004). Clinical implications of T cell receptor repertoire analysis after allogeneic stem cell transplantation. Hematol. 9:189-198.
8. Wlodarski M, Schade A, Maciejewski JP. (2005). TCR analysis in T-LGL leukemia. Haematol. J (in press).
9. Maciejewski JP, O'Keefe C, Gondek L and Wlodarski M. (2005). Immune-mediated bone marrow failure syndromes of progenitor and stem cells-molecular analysis of cytotoxic T cell clones. Folia Histochemica (in press).
10. Maciejewski JP and Risitano AM. (2005). Aplastic anemia: management of adult patients. Blood (suppl) (in press).
11. Sloand E, Kim S, Fuhrer M, Risitano AM, Nakamura R, Maciejewski JP, Young NS (2002) Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities. Blood 100, 4427-4432
12. Zeng W, Maciejewski JP, Chen G, Risitano AM, Kirby M, Young NS. (2002) Selective Reduction of NKT Cells in the Bone marrow of aplastic Anemia and myelodysplastic syndrome. Brit. J Hematol. 119, 803-809.
13. Holada K, Simek J, Young NS, Maciejewski JP, Vostal JG. (2002) Distinct pattern of of prion protein expression in platelets derived from nortmal individuals and patients with paroxysmal nocturnal hemoglobinuria. Blood 100, 341-343.
14. Selleri C, Maciejewski JP, Catalano LC, Ricci P, Andretta C, Luciano L, Rotoli B (2002). Effects of cyclosporine on the hematopoietic and immune function in patients with hypoplastic myelodysplasia: in vitro and in vivo studies. Cancer 95, 1911-1923.
15. Saunthararajah Y, Nakamura R, Nam JM, Robyn J, Loberiza F, Maciejewski JP, Simonis T, Molldrem J, Young, NS, Barrett JA. (2002) HLA DR15 (DR2) is over-represented in myelodysplastic syndrome and aplastic anemia, and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 100, 1570-1574
16. Tisdale JF, Maciejewski, JP, Nunez O, Rosenfeld SJ, Young, NS (2002). Late Complications Following High-Dose Cyclophosphamide (Cy) as Initial Treatment for Severe Aplastic Anemia (SAA) Follow up of a Randomized Trial. Blood 100, 4668-4670
17. Maciejewski JP, Rivera C, Dunn D, Young NS. (2002) Clinical features of the relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria. Brit J Hematol. 115, 1015-1022
18. Maciejewski JP, Ristano AM, Wisch L, Geller N, Barrett JS, Young, NS. (2002) A pilot study of the recombinant soluble recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein in patients with myelodysplastic syndrome. Br. J. Hematol. 117, 119-126
19. Maciejewski JP, Risitano A, Nunez O, Young NS (2002) Evolution of secondary karyotypic abnormalities in patients with aplastic anemia. Blood 99, 3129-35
20. CHen, G, Kirby M, Young NS and Maciejewski JP. (2002) Superior growth of glycophosphatidylinositol-anchored protein-deficient progenitor cells in vitro is due to the higher apoptotic rate of progenitors with normal phenotype in vivo. Experimental Exp Hematol 30, 774-782
21. Kook H, Zeng W, Wlodarski M, Risitano A., Lotteman C, Young NS, Maciejewski JP. (2002) Changes in VB-repertoire in aplastic anemia. Effects of multiple immunosuppressive regimens. Blood 99, 3668-75.
22. Risitano A, Kook H, Zeng Z, Chen G, Young NS, Maciejewski JP. (2002) Significance of oligoclonal and polyclonal expansion within CD8 and CD4 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by VB CDR3 Spectratyping and Flow Cytometry. Blood 100, 178-183
23. Holada K, Simak J, Risitano AM, Maciejewski JP, Young NS and Vostal JG (2002). Activated platelets of patients with paroxysmal nocturnal hemoglobinuria express cellular prion protein. Blood 100:341-343
24. Selleri C, Maciejewski JP, Catalano L, Ricci P, Andretta C, Luciano L, Rotoli B (2002). Effect of cyclosporine on hematoppoietic and immune functions in-patients with hypoplastic myelodysplasia. Cancer 95, 1911-22
25. Maciejewski JP, Sloand E, Nunez O, Young N. (2003). Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood 102:3584-3586.
26. Risitano A.M., Holada K., Chen G., Simek J., Vostal J.G., Young N.S., Maciejewski J.M. (2003) CD34+ cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of normal prion protein (Prpc). Exp. Hematol. 31, 65-72
27. Maciejewski JP and Selleri C. (2003). Evolution of clonal cytogenetic abnormalities in aplastic anemia. Leukemia Lymphoma, 45:433-440
28. Lee JJ, Nam CE, Kook H, Maciejewski JP, Kim YK, Chung IJ, Park KS, Lee IK, Hwang TJ, Kim HJ. (2003). Constitution and telomere dynamics of bone marrow stromal cells in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 32:947-52
29. Sloand EM, Fuhrer M, Keyvanfar K, Mainwaring L, Maciejewski JP, Wang Y, Johnson S, Barrett AJ, Young NS. (2003) Cytogenetic abnormalities in paroxysmal nocturnal haemoglobinuria usually occur in haematopoietic cells that are glycosylphosphatidylinositol-anchored protein (GPI-AP) positive.Br J Haematol.:23:173-6.
30. Selleri, C, Maciejewski JP, Mountouri N, Patricia Ricci, Visconte V, Serio B, Luciana L, Rotoli B (2003). Involvement of nitric oxide in farnesil transferase inhibitor-mediated apoptosis in chronic myeloid leukemia cells. Blood 102:1490-1498
31. Beck RC, Stahl S, O'Keefe CL, Maciejewski JP, Theil KS and His ED. (2003). Detection of mature T cell leukemias by flow cytometry using anti-t cell receptor V? antibodies. Am. J Clin Path 120:785-794.
32. Chen G, Kook H, Zeng W, Young NS and Maciejewski JP. (2003). Is there a direct effect of antithymocyte globulin on hematopoiesis? J. Hematol 5:255-261.
33. Khaiboullina SF, Maciejewski JP, Crapnell K, Pari GS, Zanjani ED, St.Jeor S (2004) Human cytomegalovirus persistence in bone marrow progenitor cells from healthy donors and after in vitro infection. Br J Haematol. 126:410-417.
34. Risitano AM, Maciejewski JP, Green S, Plasilova M, Zeng W, and Young NS. (2004). In vivo dominant immune responses in aplastic anemia patients: molecular tracking of putatively pathogenic T cell clones by TCR?-CDR3 sequencing. Lancet 364:355-364.
35. O'Keefe CL, Sobecks, RM, Rodriguez A, Bell, K, Kuczkowski E, Bolwell BJ and Maciejewski, JP. (2004). Molecular TCR diagnostics can be used to identify shared clonotypes after allogeneic hematopoietic stem cell transplantation. Exp. Hematol. 32,1010-1022
36. O'Keefe CL, Plasilova M, Risitano AM, Rodriguez AR, Wlodarski M, Young NS and Maciejewski JP. (2004). Molecular analysis of T cell receptor clonotypes in LGL - a clonal model for polyclonal responses. J Immunol 172, 1960-1969
37. Plasilova M, Risitano AM, O'Keefe CL, Rodriguez A, Wlodarski, M and Maciejewski, JP. (2004). Shared and individual specificities of immunodominant cytotoxic T cell clones in paroxysmal nocturnal hemoglobinuria as determined by molecular analysis. Exp. Hematol 32:261-269
38. Kim JA, Rao P, Graor H, Rothchild K, O'Keefe C and Maciejewski JP. (2004). CDR3 spectratyping identifies clonal expansion within T-cell subpopulations that demonstrate therapeutic antitumor activity. Surgery 136:295-302.
39. Kearns WG, Sutton JF, Maciejewski JP, Young NS, Liu JM. (2004). Genomic instability in bone marrow failure syndromes. Am J Hematol 76:220-224.
40. Sloand EM, Mainwaring L, Keyvanfar K, Chen J, Maciejewski J, Klein HG, Young NS. (2004). Evidence for transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria. Blood 104:3782-8
41. Khaiboullina SF, Rizvanov AA, Otteson E, Miyazato A, Maciejewski J, St Jeor S. (2004). Regulation of cellular gene expression in endothelial cells by sin nombre and prospect hill viruses. Viral Immunol. 17:234-251.
42. Chen G, Zeng W, Miyazato A, Billings E, Maciejewski JP, Kajigaya S, Sloand EM, Young NS. (2004). Distinctive gene expression profiles of CD34 cells from patients with myelodysplastic syndrome characterized by specific chromosomal abnormalities. Blood 104:4210-8
43. Risitano RM, Maciejewski JP,Muranski,P Wlodarski M, O'Keefe Ch, Sloand EM and Young NS (2005) Large granular lymphocyte (LGL)-like clonal expansions in paroxysmal nocturnal hemoglobinuria (PNH) patients. Leukemia 19:217-222
44. Chen G, Zeng W, Maciejewski JP, Keyvanfar K, Billings EM, Young NS (2005) Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in normal" phenotype cells. Leukemia 19, 862-868
45. Howe EC, Wlodarski M, Ball E, Maciejewski JP (2005) Killer immunoglobulin-like receptor genotype in immune-mediated bone marrow failure syndrome. Exp. Hematol. 33:1357-1362
46. Beck R, Wlodarski M, Gondek L, Theil KS, Tuthill R, Bolwell B, and Maciejewski JP (2005) Efficient identification of T-cell clones associated with graft-versus-host disease in target tissue allows for subsequent detection in peripheral blood. Brit J. Hematol. 129, 411-4119
47. Wlodarski M, O'Keefe Ch, Howe E, Rodriguez A, Warshawsky I, Loughran T, Maciejewski JP (2005) Pathologic clonal cytotoxic T cell responses - non random nature of the T cell receptor restriction in large granular lymphocyte leukemia. Blood 106, 2769-80
48. Bego M, Maciejewski JP, Khaiboullina S, Pari G and St Jeor S. (2005). Characterization of an anti-sense transcript spanning the UL81-82 locus of HCMV. J. Vir 79:11022-34.
49. Dean R, Masci P, Pohlman B, Andresen S, Serafino S, Sobecks R, Kuczkowski E, Curtis J, Maciejewski JP, Rybicki L, Kalaycio M, Hsi E, Theil K and Bolwell BJ. (2005) Dendritic cells in autologous hematopoietic stem cell transplantation for diffuse large B-cell lymphoma: graft content and post transplant recovery predict survival. Bone Marrow Transplant 36(12):1049-52.
50. Zeng W, Miyazato A, Chen G, Kajigaya S, Young NS and Maciejewski JP. (2006) Interferon-{gamma}-induced gene expression in CD34 cells. Identification of pathologic cytokine-specific signature profiles. Blood 107, 167-175.
51. Sloand EM, Scheinberg P, Maciejewski JP and Young N. (2005). Successful treatment of pure red cell aplasia with anti-IL-2 receptor antibody (Daclizumab). Annals of Int. Med (in press).
52. Maciejewski JP and Risitano AM. (2005). Aplastic anemia: management of adult patients. Hematology (Am Soc Hematol Educ Program), 110-7.
53. Schade AE, Powers J, Wlodarski MW and Maciejewski JP. (2005). Phosphatidylinositol-3-phosphate kinanse pathway activation protects leukemic large granular lymphocytes from undergoing homeostatic apoptosis. Blood (in press).
54. Wlodarski M, Gondek G, Nearman N, Rodriguez A, Plasilova M, Sekeres M, and Maciejewski JP. (2005) Molecular strategies for detection and quantitation of clonal cytotoxic T cell responses in myelodysplastic syndrome and aplastic anemia. Blood (in press).
55. Bego M, , Khaiboullina S, Pari G, Maciejewski JP and St Jeor S. (2006). Humoral response to CMV latency acssociated transcript UL81-82ast.. J. Vir (submitted)
