Letter to the Editor
Ann Lab Med 2021; 41(3): 328-332
Published online May 1, 2021 https://doi.org/10.3343/alm.2021.41.3.328
Copyright © Korean Society for Laboratory Medicine.
Promyelocytic Blast Phase of Chronic Myeloid Leukemia, BCR-ABL1-Positive: Points to be Considered at Diagnosis
1Department of Laboratory Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea; 2Samkwang Medical Lab, Seoul, Korea
Correspondence to: Bohyun Kim, M.D., Ph.D.
Department of Laboratory Medicine, Soonchunhyang University Cheonan Hospital, 31 Soonchunhyang 6-gil, Dongnam-gu, Cheonan 31151, Korea
Tel: +82-41-570-3571, Fax: +82-41-572-2316
Progression to promyelocytic blast phase (BP) in chronic myeloid leukemia (CML),
A 35-year-old male patient with leukocytosis (60.55 × 109/L) was admitted to Soonchunhyang University Cheonan Hospital in March 2017. Bone marrow (BM) study revealed hypercellularity with myeloid and megakaryocytic hyperplasia.Chromosomal analysis revealed 46,XY,t(9;22)(q34;q11.2). The quantity of major
Two years later (in April 2019), his peripheral blood (PB) smear revealed marked leukocytosis (164.42 × 109/L), anemia, and thrombocytosis, with 2% blasts and left-shifted neutrophilic maturation. Newly developed hepatosplenomegaly was detected. BM finding was similar to the previous results, but diffuse myelofibrosis was additionally detected. The result of chromosomal analysis was same as before, but the quantity of
After two months of dasatinib therapy, the patient complained of oral bleeding. PB smear showed leukocytosis with 97% abnormal promyelocytes, anemia, and thrombocytopenia. The disseminated intravascular coagulation (DIC) score calculated using the International Society on Thrombosis and Haemostasis scoring system was 9 (Table 1) . BM study revealed 96.20% abnormal promyelocytes (Fig. 1A). Immunophenotype of abnormal promyelocytes was consistent with acute promyelocytic leukemia (APL). Chromosomal analysis revealed 46,XY,t(9;22)(q34; q11.2),t(15;17)(q24;q21). The quantity of
Figure 1. Results of BM study, RT-qPCR, and FISH assay at the diagnosis of blast phase of CML. (A) Abnormal promyelocytes on a BM aspirate smear (Wright–Giemsa stain, × 1,000). (B) RT-qPCR analysis of
BCR-ABL1translocation (HemaVision-28N, DNA Diagnostic, Risskov, Denmark), showing a 397-bp band in the M6B split-out PCR and a 353-bp band in the M8C split-out PCR, indicating BCR-ABL1(b3a2) and PML-RARA(bcr1 isoform) fusion transcripts. (C and D) FISH using a break-apart probe for BCR-ABL1and PML-RARAfusion genes (Cytocell, Cytocell Ltd, Oxford Gene Technology, Cambridge, UK) showed two fusion signals, one green and one red, suggesting both BCRABL1and PML-RARArearrangements.
Abbreviations: BM, bone marrow; CML, chronic myeloid leukemia; FISH, fluorescence
in-situhybridization; RT-qPCR, quantitative reverse-transcription PCR.
We found three reported cases of promyelocytic BP of CML with
The following mechanisms have been suggested for disease progression from CML, CP to common BP despite TKI therapy: competitive advantage to Philadelphia-negative cells with genetic instability, chromosomal aberrations, and mutations of tumor suppressor genes and oncogenes [5, 6]. Specific risk factors for disease progression to promyelocytic BP of CML have not been identified so far. Few studies have suggested selective suppression of the Philadelphia-positive clone by TKI and TKIinduced chromosomal aberrations [1, 3]. The longer the delay in starting TKI therapy, the more the cells exposed to genomic instability . This finding suggests that
Among the reported four patients, three showed bleeding symptoms and accompanying DIC. Coagulopathy is frequently observed in APL and is associated with early death . Thus, when CML patients show bleeding symptoms, early detection of disease progression and starting adequate treatment immediately are critical.
Few studies have reported APL with both
In conclusion, disease progression of CML to promyelocytic BP should be considered when (1)
Kim B designed the study and wrote the manuscript. Chi HY analyzed and interpreted the molecular tests. Yoon YA and Choi YJ interpreted the results of laboratory tests and participated in discussion. All authors read and approved the final manuscript.
CONFLICTS OF INTEREST
This study was supported by the Soonchunhyang University Research Fund.
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