The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.
Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.
The Philadelphia (Ph) chromosome, or t(9;22), is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene (previously ABL) on chromosome 9. CML is clinically characterized by three distinct phases: chronic, accelerated, and blast phase. Blast crisis is characterized by the rapid expansion of a population of differentiation arrested blast cells (myeloid or lymphoid cells population), with secondary chromosomal abnormalities present. We report a case of myeloid blast crisis of CML resistant to imatinib mesylate and chemotherapy. By use of cytogenetic, fluorescence in situ hybridization, and comparative genomic hybridization methods, we identified a cluster of BCR-ABL amplification on inverted duplication of the Ph chromosome with t(3;21)(q26;q22) and increased genomic levels of the RUNX1 gene (previously AML1). The t(3;21)(q26;q22) is a recurrent chromosomal abnormality in some cases of CML blast phase and in treatment-related myelodysplastic syndrome and acute myeloid leukemia. Amplification or copy number increase of RUNX1 has been reported in childhood acute lymphoblastic leukemia. Our study indicated that the progenitor of CML was BCR-ABL dependent through the amplification of Ph chromosome as a mechanism of resistance to imatinib therapy. The coexistence of BCR-ABL and t(3;21)(q26;q22) with RUNX1 rearrangement might play a pivotal role in the CML blast transformation.