Chronic Myelogenous Leukaemia with Additional Cytogenetic Abnormalities Transformation into Blastic Crisis

Authors

  • Gowrisankari Navaretnam nstitute of Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur
  • Toh CT
  • Nor Rizan K
  • Zahidah AS
  • Wan Khairull DWM
  • Siti Aishah L Department of Pathology, Raja Permaisuri Bainun Hospital, Ipoh
  • Kamini K Department of Internal Medicine, Raja Permaisuri Bainun Hospital, Ipoh
  • Ermi Neiza S Institute of Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur
  • Norafiza Y
  • Ezalia E
  • Yuslina MY

Keywords:

Chronic Myelogenous Leukaemia, t(9, 22)(q34, q11), E255K BCR-ABL kinase domain mutation

Abstract

Chronic Myelogenous Leukaemia (CML) is a myeloproliferative neoplasm (MPN) with clonal proliferation of all myeloid cell lines which originates in an abnormal pluripotent bone marrow stem cell. CML is characterized by the t(9;22)(q34;q11) translocation in Philadelphia (Ph) chromosome forming BCR-ABL1 fusion gene. Additional cytogenetic abnormality in CML is associated with disease progression, resistance to tyrosine kinase inhibitors (TKI) and impact on prognosis of the illness. We report a case of a young male diagnosed in 2017 with CML with acquired additional t(3;21)(q26.2;q22) mutation. He developed resistance to treatment with first and second-generation TKI and progressed to blastic crisis early on. Patient was found to have E255K BCR-ABL kinase domain mutations. Apart from CML, BCR-ABL gene fusion caused by t(9;22) translocation can also be found in ALL and AML. Diseases caused by this fusion gene are depended on the breakpoint location on the BCR gene. The most common breakpoint location in CML is in the major cluster M-BCR that produces p210 protein. Breakpoint in the minor area m-BCR will produce p190 protein mostly related to ALL for cases with positive Philadelphia chromosome. Additional cytogenetics abnormalities are strongly associated with an early progression to blastic crisis, but their prognostic impact is yet to be defined. However, patients with E255K mutation have a poor prognosis, regardless of the stage of the disease at detection. Furthermore, the E255K mutation has been associated with imatinib and nilotinib resistance in patients with CML. Hence, cytogenetic and molecular screening is important not only during diagnosis of CML but also during management to improve patient’s prognosis and survival rate.

References

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Published

2022-01-06

Issue

Vol. 6 No. 2 (2021): Special Issue (Dec 2021)

Section

Journal of Biomedical and Clinical Sciences

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