A Unique Case of BCR::ABL1-Positive Chronic Myeloid Leukemia (CML) with Concurrent Chronic Myelomonocytic Leukemia (CMML)-Like Features: A Masked Composite Condition or Disease Progression?

Document Type

Conference Proceeding

Publication Date

6-1-2024

Publication Title

J Mol Diagn

Abstract

Introduction: Chronic myeloid leukemia (CML) is characterized by the presence of the BCR::ABL1 gene fusion resulting from t(9;22) translocation. The bone marrow (BM) typically exhibits hypercellularity with prominent granulocytic proliferation, reflecting a maturation pattern similar to peripheral blood. Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm (MDS/MPN), characterized by persistent monocytosis, various somatic mutations, and absence of BCR::ABL1. This case represents CML, BCR::ABL1 p210, and it is complicated by the presence of CMML-like features, bringing forth the consideration of a masked composite condition or disease progression. Methods: Peripheral blood (PB) and BM samples were obtained from the patient after informed consent. Chromosome analysis and fluorescence in-situ hybridization (FISH) were conducted on BM aspirates, while RT-PCR was performed on PB. Myeloid next-generation sequencing was carried out on DNA extracted from BM. Results: A 61-year-old male presented with leukocytosis (208.9 × 109/L) and absolute monocytosis (2.03 × 109/L) and relative (1%). BM biopsy revealed marked hypercellularity, prominent granulocytic proliferation with granulocytic dysplasia, ring sideroblasts (>15%, add-on iron stain months after initial diagnosis), dwarf megakaryocytes, and 7% blasts. PB showed neutrophilic dysplasia and 11% blasts. Chromosome analysis and FISH confirmed the presence of t(9;22) and BCR::ABL1 fusion. RT-PCR detected the BCR::ABL1 p210 transcript at 31.727% International Scale (IS), consistent with CML, BCR::ABL1 positive. Treatment with tyrosine kinase inhibitors (dasatinib, then bosutinib) normalized white blood cell count, but absolute monocytosis (>0.5 x 109/L) and relative (>10%) persisted. Follow-up RT-PCR showed a gradual reduction of BCR::ABL1 p210 to 10.99% and 2.8482% at 6- and 10-month intervals, respectively. BM biopsy 1 year after diagnosis demonstrated hypercellularity (100%), trilineage dysplasia, 4% blasts, mild marrow reticulin fibrosis (myelofibrosis grade 1/3), and BCR::ABL1 p210 (IS: 1.3651%). Pathogenic SF3B1 K700E (variant allele frequency, 41.67%), TET2 Q530* (43.15%), TET2 S714* (40.95%), and ASXL1 G646fs (5.55%) mutations were found, but ABL kinase domain mutations were negative. The clinical course demonstrated refractory CML and CMML characteristics. Subsequently, the patient underwent haploperipheral stem cell transplantation (PSCT). Conclusions: The patient's clinical course, including anemia and absolute monocytosis (>0.5 x 109/L) and relative (>10%) in PB starting 3 years before the onset of CML, suggests an uncommon manifestation of CML, possibly preceded by masked CMML, and less likely CMML-like disease progression. Allogeneic PSCT is a promising treatment for this refractory CML complicated by CMML.

Volume

26

Issue

6

First Page

S32

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