• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Feb 1, 1996; 97(3): 755–760.
PMCID: PMC507113

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

Abstract

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

Full Text

The Full Text of this article is available as a PDF (234K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pui CH, Crist WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr. 1994 Apr;124(4):491–503. [PubMed]
  • Rivera GK, Raimondi SC, Hancock ML, Behm FG, Pui CH, Abromowitch M, Mirro J, Jr, Ochs JS, Look AT, Williams DL, et al. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. Lancet. 1991 Jan 12;337(8733):61–66. [PubMed]
  • Pui CH. Childhood leukemias. N Engl J Med. 1995 Jun 15;332(24):1618–1630. [PubMed]
  • Manabe A, Coustan-Smith E, Behm FG, Raimondi SC, Campana D. Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute lymphoblastic leukemia. Blood. 1992 May 1;79(9):2370–2377. [PubMed]
  • Manabe A, Murti KG, Coustan-Smith E, Kumagai M, Behm FG, Raimondi SC, Campana D. Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells. Blood. 1994 Feb 1;83(3):758–766. [PubMed]
  • Campana D, Manabe A, Evans WE. Stroma-supported immunocytometric assay (SIA): a novel method for testing the sensitivity of acute lymphoblastic leukemia cells to cytotoxic drugs. Leukemia. 1993 Mar;7(3):482–488. [PubMed]
  • Manabe A, Coustan-Smith E, Kumagai M, Behm FG, Raimondi SC, Pui CH, Campana D. Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia. Blood. 1994 Apr 1;83(7):1731–1737. [PubMed]
  • Kumagai M, Coustan-Smith E, Murray DJ, Silvennoinen O, Murti KG, Evans WE, Malavasi F, Campana D. Ligation of CD38 suppresses human B lymphopoiesis. J Exp Med. 1995 Mar 1;181(3):1101–1110. [PMC free article] [PubMed]
  • Young L, Alfieri C, Hennessy K, Evans H, O'Hara C, Anderson KC, Ritz J, Shapiro RS, Rickinson A, Kieff E, et al. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. [PubMed]
  • Evans WE, Rodman J, Relling MV, Crom WR, Rivera GK, Crist WM, Pui CH. Individualized dosages of chemotherapy as a strategy to improve response for acute lymphocytic leukemia. Semin Hematol. 1991 Jul;28(3 Suppl 4):15–21. [PubMed]
  • Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. [PMC free article] [PubMed]
  • Lahti JM, Xiang J, Heath LS, Campana D, Kidd VJ. PITSLRE protein kinase activity is associated with apoptosis. Mol Cell Biol. 1995 Jan;15(1):1–11. [PMC free article] [PubMed]
  • Darzynkiewicz Z, Bruno S, Del Bino G, Gorczyca W, Hotz MA, Lassota P, Traganos F. Features of apoptotic cells measured by flow cytometry. Cytometry. 1992;13(8):795–808. [PubMed]
  • Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. [PubMed]
  • Pui CH, Crist WM, Look AT. Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia. Blood. 1990 Oct 15;76(8):1449–1463. [PubMed]
  • Greaves MF. Differentiation-linked leukemogenesis in lymphocytes. Science. 1986 Nov 7;234(4777):697–704. [PubMed]
  • Korsmeyer SJ. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood. 1992 Aug 15;80(4):879–886. [PubMed]
  • Cline MJ. The molecular basis of leukemia. N Engl J Med. 1994 Feb 3;330(5):328–336. [PubMed]
  • Goldie JH, Coldman AJ. Genetic instability in the development of drug resistance. Semin Oncol. 1985 Sep;12(3):222–230. [PubMed]
  • Secker-Walker LM, Lawler SD, Hardisty RM. Prognostic implications of chromosomal findings in acute lymphoblastic leukaemia at diagnosis. Br Med J. 1978 Dec 2;2(6151):1529–1530. [PMC free article] [PubMed]
  • Trueworthy R, Shuster J, Look T, Crist W, Borowitz M, Carroll A, Frankel L, Harris M, Wagner H, Haggard M, et al. Ploidy of lymphoblasts is the strongest predictor of treatment outcome in B-progenitor cell acute lymphoblastic leukemia of childhood: a Pediatric Oncology Group study. J Clin Oncol. 1992 Apr;10(4):606–613. [PubMed]
  • Tsuchiya H, Matsuda I, Kaneko Y. Why does childhood acute lymphoblastic leukemia with hyperdiploidy show a favorable prognosis? Cancer Genet Cytogenet. 1990 Dec;50(2):273–275. [PubMed]
  • Smets LA, Slater RM, Behrendt H, Van't Veer MB, Homan-Blok J. Phenotypic and karyotypic properties of hyperdiploid acute lymphoblastic leukaemia of childhood. Br J Haematol. 1985 Sep;61(1):113–123. [PubMed]
  • Uckun FM, Sather H, Reaman G, Shuster J, Land V, Trigg M, Gunther R, Chelstrom L, Bleyer A, Gaynon P, et al. Leukemic cell growth in SCID mice as a predictor of relapse in high-risk B-lineage acute lymphoblastic leukemia. Blood. 1995 Feb 15;85(4):873–878. [PubMed]
  • Richard G, Brody J, Sun T. A case of acute megakaryocytic leukemia with hematogones. Leukemia. 1993 Nov;7(11):1900–1903. [PubMed]
  • Kumagai M, Manabe A, Coustan-Smith E, Blakley RL, Beck WT, Santana VM, Behm FG, Raimondi SC, Campana D. Use of stroma-supported cultures of leukemic cells to assess antileukemic drugs. II. Potent cytotoxicity of 2-chloro-deoxyadenosine in acute lymphoblastic leukemia. Leukemia. 1994 Jul;8(7):1116–1123. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...