ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases

Michinori Aoe, Akira Shimada, Michiko Muraoka, Kana Washio, Yoshimi Nakamura, Takahide Takahashi, Masahide Imada, Toshiyuki Watanabe, Ken Okada, Ritsuo Nishiuchi, Takako Miyamura, Kosuke Chayama, Misako Shibakura, Megumi Oda, Tsuneo Morishima

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The tyrosine kinase inhibitor (TKI) imatinib mesylate (IM) revolutionized the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL), which had showed poor prognosis before the dawn of IM treatment. However, if Ph-ALL patients showed IM resistance due to ABL kinase mutation, second-generation TKI, dasatinib or nilotinib, was recommended. We treated 4 pediatric Ph-ALL patients with both IM and bone marrow transplantation (BMT); however, 3 relapsed. We retrospectively examined the existence of ABL kinase mutation using PCR and direct sequencing methods, but there was no such mutation in all 4 diagnostic samples. Interestingly, two relapsed samples from patients who were not treated with IM before relapse did not show ABL kinase mutation and IM was still effective even after relapse. On the other hand, one patient who showed resistance to 3 TKI acquired dual ABL kinase mutations, F359C at the IM-resistant phase and F317I at the dasatinib-resistant phase, simultaneously. In summary, Ph-ALL patients relapsed with or without ABL kinase mutation. Furthermore, ABL kinase mutation was only found after IM treatment, so an IM-resistant clone might have been selected during the IM treatment and intensive chemotherapy. The appropriate combination of TKI and BMT must be discussed to cure Ph-ALL patients.

Original languageEnglish
Pages (from-to)609-615
Number of pages7
JournalInternational Journal of Hematology
Volume99
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Phosphotransferases
Pediatrics
Recurrence
Mutation
Protein-Tyrosine Kinases
Bone Marrow Transplantation
Imatinib Mesylate
Therapeutics
Clone Cells
Drug Therapy

Keywords

  • ALL
  • BCR-ABL
  • Ph
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases. / Aoe, Michinori; Shimada, Akira; Muraoka, Michiko; Washio, Kana; Nakamura, Yoshimi; Takahashi, Takahide; Imada, Masahide; Watanabe, Toshiyuki; Okada, Ken; Nishiuchi, Ritsuo; Miyamura, Takako; Chayama, Kosuke; Shibakura, Misako; Oda, Megumi; Morishima, Tsuneo.

In: International Journal of Hematology, Vol. 99, No. 5, 2014, p. 609-615.

Research output: Contribution to journalArticle

Aoe, M, Shimada, A, Muraoka, M, Washio, K, Nakamura, Y, Takahashi, T, Imada, M, Watanabe, T, Okada, K, Nishiuchi, R, Miyamura, T, Chayama, K, Shibakura, M, Oda, M & Morishima, T 2014, 'ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases', International Journal of Hematology, vol. 99, no. 5, pp. 609-615. https://doi.org/10.1007/s12185-014-1565-3
Aoe, Michinori ; Shimada, Akira ; Muraoka, Michiko ; Washio, Kana ; Nakamura, Yoshimi ; Takahashi, Takahide ; Imada, Masahide ; Watanabe, Toshiyuki ; Okada, Ken ; Nishiuchi, Ritsuo ; Miyamura, Takako ; Chayama, Kosuke ; Shibakura, Misako ; Oda, Megumi ; Morishima, Tsuneo. / ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases. In: International Journal of Hematology. 2014 ; Vol. 99, No. 5. pp. 609-615.
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