Chronic myelogenous leukemia

Current Opinion in Hematology

Volumn 3, Issue 4, 1996, Pages 303-309

  Enright, Helen ^a   McGlave, Philip B ^a  

^a UNIV OF MINNESOTA HOSP AND CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGODEOXYNUCLEOTIDE; INTERFERON;

BONE MARROW TRANSPLANTATION; CANCER SURVIVAL; CELL PROLIFERATION; CHROMOSOME 22; CHROMOSOME 9; CHRONIC MYELOID LEUKEMIA; CLONAL ANERGY; ENZYME ACTIVITY; HEMATOPOIETIC CELL; HUMAN; IMMUNE RESPONSE; PHILADELPHIA 1 CHROMOSOME; PRIORITY JOURNAL; REVIEW; STEM CELL;

EID: 0030017862     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199603040-00009     Document Type: Review

References (59)

1. Diamond J, Goldman JM, Melo JV: BCR-ABL, ABL-BCR, BCR, and ABL • genes are all expressed in individual granulocyte-macrophage colony-forming unit colonies derived from blood of patients with chronic myeloid leukemia. Blood 1995, 85:2171-2175. Granulocyte-macrophage colony-forming unit colonies from the peripheral blood of patients with CML were examined by reverse transcriptase polymerase chain reaction for expression of bcr-abl, abl-bcr, bcr, and abl genes. It was found that all four genes were simultaneously expressed in the majority of granulocyte-macrophage colony-forming unit colonies. In addition, contrary to previous reports, it was found that bcr-abl expression does not suppress transcription of the normal bcr and abl genes.
2. + cells revert to factor dependence and nontumorigenicity. Thus bcl-2 may be important in mediating the effects of bcr-abl expression in CML.
3. + cells and suggest that this activity could be exploited to eliminate CML cells from bone marrow.
4. McGahon AJ, Nishioka WK, Martin SJ, Mahboubi A, Cotter TG, Green DR: • Regulation of the Fas apoptotic cell death pathway by Abl. J Biol Chem 1995, 270:22625-22631. This study examined the potential function of abl kinase as a negative regulator of cell death. Downregulation of bcr-abl protein levels in K562 transformants expressing Fas, which are protected against Fas-mediated cell death, rendered these cells highly susceptible to Fas-induced death.
5. Cortez D, Kadlec L, Pendergast AM: Structural and signaling requirements for BCR-ABL-mediated transformation and inhibition of apoptosis. Mol Cell Biol 1995, 15:5531-5541.
6. 2/M cell cycle defect was identified with delayed transition through this phase, perhaps allowing time for DNA repair.
7. Amos TAS, Lewis JL, Grand FH, Gooding RP, Goldman JM, Gordon MY: Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiatlon and glucocorticoids. Br J Haematol 1995, 91:387-393.
8. Lisovsky MYA, Savchenko VG: Defect of stromal microenvironment in long term bone marrow cultures of patients with acute and chronic myelogenous leukemias. Leuk Lymphoma 1995, 19:145-152.
9. Bhatia R, McGlave PB, Verfaillie CM: Treatment of marrow stroma with •• interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha. J Clin Invest 1995, 96:931-939. The interactions between bone marrow stroma and β-1 integrin-mediated adhesion of CML progenitors and the influence of interferon alpha on these interactions were studied. Pretreatment with interferon alpha of marrow stroma increased adhesion of CML progenitors. Receptors for α4β1 and α5β1 integrins were involved in the enhanced adhesion of CML progenitors. The upregulation of CML integrin function by interferon alpha may be mediated via stromal production of macrophage inflammatory protein 1α. These findings may be relevant to the restoration of normal hematopoiesis in CML by interferon alpha.
10. + stromal macrophages.
11. Ghaffari S, Dougherty GJ, Lansdorp PM, Eaves AC, Eaves CJ: Differentiation-associated changes in CD44 isoform expression during normal hematopoiesis and their alteration in chronic myeloid leukemia. Blood 1995, 86:2976-2985.
12. Renshaw MW, McWhirter JR, Wang JY: The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation. Mol Cell Biol 1995, 15:1286-1293.
13. Agarwal R, Doren S, Hicks B, Dunbar CE: Long-term culture of chronic myelogenous leukemia marrow cells on stem cell factor-deficient stroma favors benign progenitors. Blood 1995, 85:1306-1312.
14. Chasty RC, Lucas GS, Owen-Lynch PJ, Pierce A, Whetton AD: Macrophage inflammatory protein-1a receptors are present on cells enriched for CD34 expression from patients with chronic myeloid leukemia. Blood 1995, 86:4270-4277.
15. Serra A, Gottardi E, Ragione FD, Saglio G, Iolascon A: Involvement of the cyclin-dependent kinase-4 inhibitor (CDKN2) gene in the pathogenesis of lymphoid blast crisis of chronic myelogenous leukaemia. Br J Haematol 1995, 91:625-629.
16. Sill H, Goldman JM, Cross NCP: Homozygous deletions of the p16 • tumor-suppressor gene are associated with lymphoid transformation of chronic myeloid leukemia. Blood 1995, 85:2013-2016. Thirty-four patients with CML in blast crisis were examined for deletion of p16. Homozygous deletion was identified in 50% of patients with CML in lymphoid blast crisis but not in patients with myeloid blast crisis. In addition, sequential studies showed that p16 deletion was acquired, at least in some cases, at the time of transformation to blast crisis.
17. Hehlmann R, Heimpel H, Hasford J, Kolb HJ, Pralle H, Hossfeld DK, Quiber W, Löffler H, Hochhaus A, Heinze B, et al.: Randomized comparison of interferon-α with busulfan and hydroxyurea in chronic myelogenous leukemia. Blood 1994, 84:4064-4077.
18. Italian Cooperative Study Group on Chronic Myeloid Leukemia: Interferon alfa-2a as compared with conventional chemotherapy for the treatment of chronic myeloid leukemia. N Engl J Med 1994, 330:820-825.
19. + cells. The median survival for the entire group of patients was 89 months. Achievement of a major cytogenetic response, when examined as a time-dependent variable and also by landmark analysis dated from 12 months into therapy, was associated with a statistically significant improvement in survival (P< 0.001).
20. Allen NC, Richards SM, Shepherd PC: UK Medical Research Council •• randomized, multicentre trial of interferon-alpha ni for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. The UK Medical Research Council's Working Parties for Therapeutic Trials in Adult Leukaemia. Lancet 1995, 345:1392-1397. A report of 587 patients with CML in chronic phase randomly assigned to receive either interferon alpha (n = 293) or chemotherapy using busulfan or hydroxyurea (n = 294). Patients receiving interferon had a median survival of 61 months compared with 41 months for those who did not receive interferon (P = 0.0009). Patients who had a cytogenetic response to interferon survived significantly longer than those not responding. However, even patients with a poor response to interferon had equivalent survival to patients receiving chemotherapy.
21. Enright H, Daniels K, Arthur DC, Dusenbery KE, Kersey JH, Kim T, Miller •• WJ, Ramsay NKC, Vercellotti GM, Weisdorf DJ, McGlave PB: Related donor marrow transplant for chronic myeloid leukemia: patient characteristics predictive of outcome. Bone Marrow Transplant 1996, 17:537-542. Pretransplant characteristics of 137 consecutive patients undergoing related donor marrow transplantation for CML were analyzed to determine their association with outcome. Factors independently associated with an increased risk of relapse or death were increased patient age and a longer interval between diagnosis and transplantation. For patients undergoing transplantation within 1 year of diagnosis, the 5-year disease-free survival was 51% compared with 34% for those patients undergoing transplantation beyond 1 year from diagnosis. The risk of relapse (5-year estimate, 20%) was also independently and significantly increased in association with a longer interval from diagnosis to transplantation.
22. Beelen DW, Graeven U, Elmaagacli AH, Niederle N, Kloke O, Opalka B, •• Schaefer UW: Prolonged administration of interferon-α in patients with chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia before allogeneic bone marrow transplantation may adversely affect transplant outcome. Blood 1995, 85:2981-2990. Report of 133 consecutive patients with first chronic-phase CML who received HLA-identical family (n = 103) or alternative donor marrow (n = 30). Prior interferon alpha administration, received by 38% of patients, was associated with a 2.5-fold lower likelihood of 5-year overall survival and a 2.3-fold lower likelihood of disease-free survival compared with patients who received only hydroxyurea or busulfan therapy. There was a 2.5-fold higher transplant-related mortality and a 3.1-fold higher incidence of fatal posttransplantation infections among patients who received interferon. Among patients receiving donor marrow other than HLA-identical family marrow, graft failure occurred only in patients previously treated with interferon, occurring in 28% of 17 patients compared with 0% of 13 patients who received hydroxyurea or busulfan.
23. Kantarjian HM, Talpaz M: Interferon-alpha therapy in chronic myelogenous leukemia: questions related to the German randomized trial [letter]. Blood 1995, 85:3000-3002.
24. Ohnishi K, Ohno R, Tomonaga M, Kamada N, Onozawa K, Kuramoto A, • Dohy H, Mizoguchi H, Miyawaki S, Tsubaki K, et al.: A randomized trial comparing interferon-α with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood 1995, 86:906-916. This multicenter randomized study examined 117 newly diagnosed patients with CML in chronic phase. Patients were randomly assigned to receive either interferon alpha or busulfan. Complete hematologic remission was achieved in 39% of interferon alpha-treated patients and 54% of busulfan-treated patients. A complete cytogenetic response was seen in 9% of patients treated with interferon alpha and 2.5% of patients treated with busulfan. Five-year survival for interferon-treated patients (54%) was significantly improved compared with patients treated with busulfan (32%) (P = 0.029). Similarly, a longer duration of chronic phase was seen in interferon alpha-treated patients achieving a complete, partial, or minor cytogenetic response.
25. Ochs L, Shu XO, Miller J, Enright H, Wagner J, Filipovich A, Miller W, Weisdorf D: Late infections after allogeneic bone marrow transplantation: comparison of incidence in related and unrelated donor transplant recipients. Blood 1995, 86:3979-3986.
26. Davies SM, Shu XO, Blazar BR, Filipovich AH, Kersey JH, Krivit W, • McCullough J, Miller WJ, Ramsay NKC, Segall M, Wagner JE, Weisdorf DJ, McGlave PB: Unrelated donor bone marrow transplantation: influence of HLA A and B incompatibility on outcome. Blood 1995, 86:1636-1642. The results of 211 consecutive unrelated donor marrow transplantations (including 87 patients with CML) performed at a single institution were analyzed to determine the influence of histoincompatibility on outcome. Older age and HLA A or B serologic mismatch were shown to have independent adverse effects on survival after unrelated donor marrow transplantation. In particular, adults receiving marrow with a major HLA serologic mismatch had significantly decreased survival compared with those receiving matched marrow.
27. Spencer A, Szydlo RM, Brookes PA, Kaminski E, Rule S, van Rhee F, Ward KN, Hale G, Waldmann H, Hows JM, Batchelor JR, Goldman JM: Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient. Blood 1995, 86:3590-3597.
28. 9/L was 15.5 days. Long-term engraftment was seen and the incidence of acute graft-versus-host disease was not greater than expected from bone marrow transplantation.
29. Kalhs P, Schwarzinger I, Anderson G, Mori M, Clift RA, Storb R, Buckner CD, Appelbaum FR, Hansen JA, Sullivan KM: A retrospective analysis of the long-term effect of splenectomy on late infections, graft-versus-host disease, relapse, and survival after allogeneic marrow transplantation for chronic myelogenous leukemia. Blood 1995, 86:2028-2032.
30. Gratwohl A, Hermans J, Appertey J, Arcese W, Bacigalupo A, Bandini G, • di Bartolomeo P, Boogaerts M, Bosi A, Carreras E, et al. for the Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation: Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Blood 1995, 86:813-818. This report from the European Group for Blood and Marrow Transplantation analyzed outcomes for 1294 patients undergoing allogeneic donor transplantation for CML in first chronic phase. Day 100 mortality and overall transplant-related mortality was increased according to the grade of severity of acute graft-versus-host disease, with significant differences between those developing grades 0-I versus III-IV. However, relapse incidence was decreased for patients with more advanced acute graft-versus-host disease. This study supports the use of grading of acute graft-versus-host disease for analysis of subsequent transplant outcome.
31. Hessner MJ, Endean DJ, Casper JT, Horowitz MM, Keever-Taylor CA, Roth • M, Flomenberg N, Drobyski WR: Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia reactivity after T-cell-depleted allogeneic marrow transplantation for chronic myelogenous leukemia. Blood 1995, 86:3987-3996. This report details the use of unrelated donor T-cell-depleted marrow transplantation for patients with CML and compares their outcome with patients receiving HLA-identical sibling marrow. Patients undergoing transplantation in accelerated phase or blast crisis had equally high relapse rates regardless of whether they received HLA-identical sibling donor or unrelated donor marrow. Unrelated donor marrow recipients undergoing transplantation in chronic phase had a significantly lower incidence of relapse than recipients of HLA-identical sibling marrow (8% vs 47%; P = 0.002).
32. Radich JP, Gehly G, Gooley T, Bryant E, Clift RA, Collins S, Edmands S, •• Kirk J, Lee A, Kessler P, Schoch G, Buckner CD, Sullivan KM, Appelbaum FR, Thomas ED: Polymerase chain reaction detection of the bcr-abl fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood 1995, 85:2632-2638. Report of 346 patients with CML who were studied for the presence of the bcr-abl transcript following marrow transplantation by polymerase chain reaction. A positive test at 3 months after transplantation was not statistically significantly associated with an increased risk of relapse compared with patients testing negative by polymerase chain reaction. However, patients testing positive 6 to 12 months after transplantation had a significantly increased risk of subsequent relapse (relative risk 26.1; P < 0.0001). These patients had a Kaplan-Meier estimate of relapse of 42% compared with 3% for patients testing negative by polymerase chain reaction (P < 0.0001). Thus close monitoring of bcr-abl after transplantation can provide useful information regarding the risks of subsequent relapse, which may lead to therapeutic intervention.
33. + cells.
34. + lymphocytes may not be critical for the graft-versus-leukemia effect obtained using donor leukocyte infusions.
35. Kolb H-J, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, • Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D, van Rhee F, Mittermueller J, de Witte T, Holler E, Ansari H for the European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia: Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995, 86:2041-2050. This large study reported 84 patients with CML who relapsed following marrow transplantation and were treated with donor lymphocyte transfusions. Complete remissions were achieved in 54 patients (73%). In addition, these remissions were durable and the probability of continuing complete remission at 3 years was 87%. This study confirms that allogeneic lymphocyte infusion can reestablish stable, continuing complete remissions in patients who relapse following transplantation.
36. 8 (n = 4). Thus donor leukocytes with a low T-cell content can result in complete remission. There was a correlation between the T-cell dose and the development of chronic graft-versus-host disease.
37. Jiang YZ, Barrett AJ: Cellular and cytokine-mediated effects of CD4-positive lymphocyte lines generated in vitro against chronic myelogenous leukemia. Exp Hematol 1995, 23:1167-1172.
38. Seong DC, Kantarjian HM, Ro JY, Talpaz M, Xu J, Robinson JR, Deisseroth • AB, Champlin RE, Siciliano MJ: Hypermetaphase fluorescence in situ hybridization for quantitative monitoring of Philadelphia chromosome-positive cells in patients with chronic myelogenous leukemia during treatment Blood 1995, 86:2343-2349. Given the growing importance of detecting and monitoring minimal residual disease in patients with CML undergoing therapy with interferon or following bone marrow transplantation, newer techniques are currently under development to optimize sensitivity and specificity of detection. One such technique is the use of hypermetaphase fluorescence in situ hybridization. This technique allows analysis of greater numbers of metaphases per sample than conventional fluorescence in situ hybridization and may be especially useful for monitoring patients treated with interferon, in whom large numbers of metaphases may be difficult to obtain.
39. Verschraegen CF, Talpaz M, Hirsch-Ginsberg CF, Pherwani R, Rios MB, Stass SA, Kantarjian HM: Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia. Blood 1995, 85:2705-2710.
40. Gaiger A, Henn T, Hörth, Geissler K, Mitterbauer G, Maisr-Dobersberger T, Greinix H, Mannhalter C, Haas OA, Lechner K, Lion T: Increase of BCR-ABL chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression. Blood 1995, 86:2371-2378.
41. Talpaz M, Kantarjian H, Liang J, Calvert L, Hamer J, Tibbits P, Durett A, Claxton D, Giralt S, Khouri I, et al: Percentage of Philadelphia chromosome (Ph)-negative and Ph-positive cells found after autologous transplantation for chronic myelogenous leukemia depends on percentage of diploid cells induced by conventional-dose chemotherapy before collection of autologous cells. Blood 1995, 85:3257-3263.
42. Kantarjian HM, Talpaz M, Hester J, Feldman E, Korbling M, Liang J, Rios MB, Smith TL, Calvert L, Deisseroth AB: Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy. J Clin Oncol 1995, 13:553-559.
43. McGlave P, Bhatia R, Verfaillie C: Cyclophosphamlde/GM-CSF priming in autotransplant therapy for CML Bone Marrow Transplant 1996, in press.
44. Podesta M, Piaggio G, Frassoni F, Sessarego M, Benvenuto F, Figari O, Pitto A, Vassallo F, Soracco M, Pollicardo N, Pungolino E, Gatti A, Prencipe E, Carella AM: Very primitive hemopoletic cells (LTC-IC) are present in Philadelphia negative cytaphereses collected during early recovery after chemotherapy for chronic myeloid leukemia (CML). Bone Marrow Transplant 1995, 16:549-555.
45. Bhatia R, McGlave PB: Autologous stem cell transplantation for the treatment of chronic myelogenous leukemia. In Advances in Bone Marrow Transplantation. Edited by Winter JN. Boston: Kluwer Academic Publishers; 1996.
46. Verfaillie CM, Miller WJ, Boylan K, McGlave PB: Selection of benign primitive hematopoletic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression. Blood 1992, 79:1003-1010.
47. Berardi AC, Wang A, Levine JD, Lopez P, Scadden OT: Functional isola•• tion and characterization of human hematopoietic stem cells. Science 1995, 267:104-108. This paper describes the purification of cells with characteristics of hematopoietic stem cells using differential responsiveness to the cytokines, kit ligand, and interleukin-3. Human bone marrow cells responsive to these cytokines were forced to undergo cell death. The subfraction remaining was found to have a stem cell immunophenotype, be highly enriched for long-term culture-initiating cells, and be capable of producing both myeloid and lymphoid progeny. A major advantage of this technique for isolation of early hematopoietic cells is that it is independent of cell sorting and of antibody binding to cell surface antigens.
48. lo population in chronic myeloid leukemia: an analysis using interphase fluorescence in situ hybridization. Blood 1995, 86:737-743.
49. Leopold LH, Shore SK, Newkirk TA, Reddy RMV, Reddy EP: Multi-unit ribozyme-medlated cleavage of bcr-abl mRNA in myeloid leukemias. Blood 1995, 85:2162-2170.
50. Maekawa T, Kimura S, Hirakawa K, Murakami A, Zon G, Abe T: Sequence specificity of the growth suppression and induction of apoptosis of chronic myeloid leukemia cells by BCR-ABL anti-sense oligodeoxynucleoside phosphorothloates. Int J Cancer 1995, 62:63-69.
51. Smetsere TF, van de Locht LT, Pennings AH, Wessels HM, de Witte TM, • Mensink EJ: Phosphorothioate BCR-ABL antisense oligonucleotides induce cell death, but fall to reduce cellular bcr-abl protein levels. Leukemia 1995, 9:118-130. The ability of phosphorothioate antisense bcr-abl oligonucleotides to induce apoptosis and reduce p210 bcr-abl levels was investigated in two CML cell lines. Although antisense oligonucleotides induced cell death, p210 bcr-abl levels were not found to be reduced in live cells after treatment with antisense oligonucleotides. Thus antisense-mediated inhibition of p210 bcr-abl mRNA and induction of apoptosis may not occur via a sequence-specific mechanism.
52. Vaerman JL, Lammineur C, Moureau P, Lewalle P, Deldime F, Blumenfeld M, Martial P: BCR-ABL antisense ollgodeoxyribonucleotides suppress the growth of leukemic and normal hematopoietic cells by a sequence-specific but nonantisense mechanism. Blood 1995, 86:3691-3896.
53. Giles RV, Spiller DG, Green JA, Clark RE, Tidd DM: Optimization of antisense ollgodeoxynucleotide structure for targeting bcr-abl mRNA. Blood 1995, 86:744-754.
54. de Fabritis P, Amadori S, Petti MC, Mancini M, Montefusco E, Picardi A, Geiser T, Campbell K, Calabretta B, Mandelli F: In vitro purging with BCR-ABL antisense oligodeoxynucleotides does not prevent haematologic reconstitution after autologous bone marrow transplantation. Leukemia 1995, 9:662-664.
55. + cytotoxic T-lymphocyte clones from a patient with severe graft-versus-host disease after allogeneic bone marrow transplantation: implications for graft-versus-leukemia reactivity. Blood 1995, 86:2821-2828.
56. Scheffold C, Brandt K, Johnston V, Lefterova P, Degen B, Schontube M, Huhn D, Neubauer A, Schmidt-Wolf IG: Potential of autologous immunologic effector cells for bone marrow purging in patients with chronic myeloid leukemia. Bone Marrow Transplant 1995, 15:33-39.
57. Bhatia R, McGlave PB: T lymphocytes cultured from chronic myelogenous leukemia bone marrow suppress autologous hematopoietic progenitors. Leukemia 1995, 9:1006-1012.
58. Cervantes F, Pierson BA, McGlave PB, Verfaillie CM, Miller JS: Autologous activated natural killer cells suppress primitive chronic myeloid leukemia progenitors in long-term culture. Blood 1996, 87:1-10.
59. Bocchia M, Wentworth PA, Southwood S, Sidney J, McGraw K, • Scheinberg DA, Sette A: Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood 1995, 85:2680-2684. A series of synthetic peptides corresponding to the junctional sequence of bcr-abl were investigated for their ability to bind to MHC class I molecules. Four peptides derived from the b3a2 breakpoint bound to the HLA class I molecules tested. This suggests the potential for human T-cell-mediated recognition of tumor-associated antigens in CML.