The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia

Hiroshi Iwama, Kazuma Ohyashiki, Junko H. Ohyashiki, Shigefumi Hayashi, Ken Kawakubo, Jerry W. Shay, Keisuke Toyama

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

BACKGROUND. Chronic myeloid leukemia (CML) is a clonal disease with specific cytogenetic changes involving the Philadelphia (Ph) translocation. The authors examined the relationship between telomere length (terminal restriction fragment [TRF]) and therapy-associated cytogenetic responses in CML patients. METHODS. The authors examined the telomere length and telomerase activity in 44 patients with Ph-positive CML in the chronic phase. TRF was determined by Southern blot analysis using the (TTAGGG)4 probe and telomerase activity was assessed by the telomeric repeat amplification protocol and fluorescent-labeled primers. RESULTS. At the time of CML diagnosis, 19 patients had TRFs within the age matched normal range (mean ± 2 x standard deviation [SD]) and the remaining 25 patients had TRFs shorter than the age-matched normal range (< mean ± 2 x SD). Hematologic findings, including leukocyte count, hemoglobin level, platelet count, and percentage of bone marrow blasts at the time of diagnosis did not significantly differ between patients with normal and shortened TRFs; however, those with shortened TRFs had high levels of telomerase activity (P = 0.045). In a group of patients treated with alpha-interferon (n = 32), those with normal TRFs had a significantly lower frequency of blast crises (P = 0.0328), a significantly higher incidence of cytogenetic responses (P = 0.0185), and a favorable prognosis (P < 0.01) compared with those with shortened TRFs. CONCLUSIONS. These findings suggest that normal TRFs in a small number of CML patients at the time of diagnosis may have a significant amount of normal stem cells remaining. The authors suggest that normal TRFs at the time of diagnosis indicate a subset of CML patients who may respond favorably to alpha-interferon therapy.

Original languageEnglish (US)
Pages (from-to)1552-1560
Number of pages9
JournalCancer
Volume79
Issue number8
DOIs
StatePublished - Apr 15 1997

Fingerprint

Telomere
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Telomerase
Therapeutics
Interferon-alpha
Reference Values
Leukemia, Myeloid, Chronic Phase
Blast Crisis
Southern Blotting
Platelet Count
Leukocyte Count
Hemoglobins
Stem Cells
Bone Marrow
Incidence

Keywords

  • chronic myeloid leukemia
  • cytogenetic response
  • interferon
  • telomerase
  • telomere

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia. / Iwama, Hiroshi; Ohyashiki, Kazuma; Ohyashiki, Junko H.; Hayashi, Shigefumi; Kawakubo, Ken; Shay, Jerry W.; Toyama, Keisuke.

In: Cancer, Vol. 79, No. 8, 15.04.1997, p. 1552-1560.

Research output: Contribution to journalArticle

Iwama, Hiroshi ; Ohyashiki, Kazuma ; Ohyashiki, Junko H. ; Hayashi, Shigefumi ; Kawakubo, Ken ; Shay, Jerry W. ; Toyama, Keisuke. / The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia. In: Cancer. 1997 ; Vol. 79, No. 8. pp. 1552-1560.
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AU - Hayashi, Shigefumi

AU - Kawakubo, Ken

AU - Shay, Jerry W.

AU - Toyama, Keisuke

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N2 - BACKGROUND. Chronic myeloid leukemia (CML) is a clonal disease with specific cytogenetic changes involving the Philadelphia (Ph) translocation. The authors examined the relationship between telomere length (terminal restriction fragment [TRF]) and therapy-associated cytogenetic responses in CML patients. METHODS. The authors examined the telomere length and telomerase activity in 44 patients with Ph-positive CML in the chronic phase. TRF was determined by Southern blot analysis using the (TTAGGG)4 probe and telomerase activity was assessed by the telomeric repeat amplification protocol and fluorescent-labeled primers. RESULTS. At the time of CML diagnosis, 19 patients had TRFs within the age matched normal range (mean ± 2 x standard deviation [SD]) and the remaining 25 patients had TRFs shorter than the age-matched normal range (< mean ± 2 x SD). Hematologic findings, including leukocyte count, hemoglobin level, platelet count, and percentage of bone marrow blasts at the time of diagnosis did not significantly differ between patients with normal and shortened TRFs; however, those with shortened TRFs had high levels of telomerase activity (P = 0.045). In a group of patients treated with alpha-interferon (n = 32), those with normal TRFs had a significantly lower frequency of blast crises (P = 0.0328), a significantly higher incidence of cytogenetic responses (P = 0.0185), and a favorable prognosis (P < 0.01) compared with those with shortened TRFs. CONCLUSIONS. These findings suggest that normal TRFs in a small number of CML patients at the time of diagnosis may have a significant amount of normal stem cells remaining. The authors suggest that normal TRFs at the time of diagnosis indicate a subset of CML patients who may respond favorably to alpha-interferon therapy.

AB - BACKGROUND. Chronic myeloid leukemia (CML) is a clonal disease with specific cytogenetic changes involving the Philadelphia (Ph) translocation. The authors examined the relationship between telomere length (terminal restriction fragment [TRF]) and therapy-associated cytogenetic responses in CML patients. METHODS. The authors examined the telomere length and telomerase activity in 44 patients with Ph-positive CML in the chronic phase. TRF was determined by Southern blot analysis using the (TTAGGG)4 probe and telomerase activity was assessed by the telomeric repeat amplification protocol and fluorescent-labeled primers. RESULTS. At the time of CML diagnosis, 19 patients had TRFs within the age matched normal range (mean ± 2 x standard deviation [SD]) and the remaining 25 patients had TRFs shorter than the age-matched normal range (< mean ± 2 x SD). Hematologic findings, including leukocyte count, hemoglobin level, platelet count, and percentage of bone marrow blasts at the time of diagnosis did not significantly differ between patients with normal and shortened TRFs; however, those with shortened TRFs had high levels of telomerase activity (P = 0.045). In a group of patients treated with alpha-interferon (n = 32), those with normal TRFs had a significantly lower frequency of blast crises (P = 0.0328), a significantly higher incidence of cytogenetic responses (P = 0.0185), and a favorable prognosis (P < 0.01) compared with those with shortened TRFs. CONCLUSIONS. These findings suggest that normal TRFs in a small number of CML patients at the time of diagnosis may have a significant amount of normal stem cells remaining. The authors suggest that normal TRFs at the time of diagnosis indicate a subset of CML patients who may respond favorably to alpha-interferon therapy.

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