Detection of dormant chronic myeloid leukemia clones in the bone marrow of patients in complete molecular remission

Alfonso Quintás-Cardama, Srdana Grgurevic, Uri Rozovski, Ping Li, Zeev Estrov, Jorge Cortes

Research output: Contribution to journalArticle

Abstract

Background Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy. Materials and Methods We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (PCR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to PCR analysis. Results Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies. Conclusion MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.

Original languageEnglish (US)
Pages (from-to)681-685
Number of pages5
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number6
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Clone Cells
Bone Marrow
Protein-Tyrosine Kinases
Polymerase Chain Reaction
Cytogenetics
Bone Marrow Cells
Recurrence
Therapeutics

Keywords

  • BCR-ABL1
  • Clonogenic assay
  • Colony
  • Minimal residual disease
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Detection of dormant chronic myeloid leukemia clones in the bone marrow of patients in complete molecular remission. / Quintás-Cardama, Alfonso; Grgurevic, Srdana; Rozovski, Uri; Li, Ping; Estrov, Zeev; Cortes, Jorge.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 13, No. 6, 01.12.2013, p. 681-685.

Research output: Contribution to journalArticle

Quintás-Cardama, Alfonso ; Grgurevic, Srdana ; Rozovski, Uri ; Li, Ping ; Estrov, Zeev ; Cortes, Jorge. / Detection of dormant chronic myeloid leukemia clones in the bone marrow of patients in complete molecular remission. In: Clinical Lymphoma, Myeloma and Leukemia. 2013 ; Vol. 13, No. 6. pp. 681-685.
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abstract = "Background Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy. Materials and Methods We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (PCR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to PCR analysis. Results Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies. Conclusion MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.",
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AU - Estrov, Zeev

AU - Cortes, Jorge

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N2 - Background Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy. Materials and Methods We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (PCR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to PCR analysis. Results Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies. Conclusion MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.

AB - Background Several methods are available to detect MRD in patients with CML in complete molecular remission (CMR) and taking tyrosine kinase inhibitor (TKI) therapy. Materials and Methods We performed clonogenic assays on mononuclear bone marrow cells from 14 patients. Of the 10 assessable samples, 6 were from patients in CMR and 4 from patients in complete cytogenetic remission but had detectable MRD using polymerase chain reaction (PCR) analysis (positive controls). At least 10 colonies per sample were microaspirated and individual colonies were subjected to PCR analysis. Results Of the 6 patients in CMR, 5 harbored breakpoint cluster region abelson (BCR-ABL1) negative colonies but in 1 sample, 1 of the 10 colonies analyzed was positive for BCR-ABL1. Of the 4 patients with evidence of MRD in peripheral blood, 2 had negative and 2 had positive BCR-ABL1 colonies. Conclusion MRD is still detectable using clonogenic assays in some patients with CML after achieving CMR using TKI therapy, which is likely responsible for relapse on TKI discontinuation. Because of the large number of single colonies that need to be analyzed, the use of clonogenic assays in clinical practice to determine the feasibility of TKI discontinuation is not recommended.

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