Origins and Underlying Mechanism of Sequential or Concurrent CLL/CML

By Dustin Samples - April 6, 2023

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative neoplasm that occurs when dysfunctional B cells accumulate in bone marrow. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that occurs when stem cells undergo a chromosomal mutation and begin a chain reaction leading to the uncontrolled proliferation of myeloid cells. Although distinct, these entities may share a common origin.

In a poster presented at the 2023 National Comprehensive Cancer Network Annual Meeting, Drs. Sujan Badal and Miriam Alamgir of the Elson S. Floyd Medicine/Providence Regional Medical Center at Washington State University, Everett, Washington, observed the rare, but previously reported, concurrence or sequential occurrence of these 2 diseases.

Badal and Alamgir identified 47 studies reporting on 62 patients diagnosed with CLL after CML, CML after CLL, or both diseases diagnosed concurrently. They sought to understand the mechanism behind the dual occurrence. After reviewing proposed mechanisms in the literature, they narrowed the potential mechanism down to 3 possibilities:

  1. Clonal origin versus distinct events,
  2. Leukemogenic effect from prior cancer or chemotherapy, and
  3. Genetic predisposition.

“Studies consistently favor distinct genetic event hypothesis. B-CLL transformation occurs in Ph chromosome negative Bcell subset,” the authors found regarding the first mechanism, clonal versus distinct event origins. There was little evidence to suggest that tyrosine-kinase inhibitors played a role in the second possibility, however the authors stated that “BCR-ABL transformed cells produce interleukin-3 (IL-3) that increases proliferation of B-lymphoid progenitor cells.” This statement suggests that secondary neoplasms may occur due to prior cancer activity or treatment. However, they believe the most likely mechanism is genetic predisposition.

“Mutations in RUNX1, CEBPA, DDX41, ETV6, GATA2 & ATM, TP53, CHEK2 possibly predisposes to CML & CLL respectively…Genetic predisposition from mutations in specific genes is being increasingly recognized as a mechanism for development of multiple hematological neoplasms,” Badal and Alamgir concluded based on review results.

Their recommendations to clinicians caring for patients with either subsequent or concurrent CLL/CML diagnoses is to “consider [the] patient’s previous treatment history; and family history for pattern of multiple neoplasms.”


Badal S, Alamgir M. Incidence & mechanisms of coexisting hematological malignancies: chronic lymphocytic leukemia and chronic myeloid leukemia – a retrospective review. Presented at the 2023 National Comprehensive Cancer Network Annual Meeting, Orlando, Florida, March 31-April 2, 2003.

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