Clonality studies can establish the single cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage specific sequences or disease-specific somatic mutations identifying the clonal population. Historically, the clonal hematopoiesis was defined using the principle of X chromosome inactivation based on observation that in circulating clonal cells only one of the active chromosomes was expressed. In the myeloproliferative neoplasms (MPNs) virtually all circulating erythrocytes, platelets and granulocytes are product of a single mutated stem cells that preferentially differentiate to myeloid rather than lymphoid lineage. Thus, clonal differentiated myeloid cells coexist in circulation with polyclonal long-lived T-lymphocytes originated prior to MPN-initiating somatic clonal event. In case of chronic lymphocytic leukemia (CLL), CLL starts in a differentiating B cell but other lymphoid lineages and myeloid cells remain polyclonal. Normal T and B-cells coexist with CLL clone, but they are diluted by the massively expanded CLL population which outnumbers the residual normal cells. Clonal hematopoiesis of undetermined potential (CHIP) has been identified by whole genome sequencing of healthy individuals. These clones contain a specific somatic mutation previously considered to be disease-defining, but they are detected only in a small proportion of circulating leukocytes, and there is no obvious suppression of normal hematopoietic stem cells. However, more studies are needed to properly define these clones and their persistence or disappearance and their relative propensity for transforming to leukemias, myeloproliferative neoplasms, or other clonal hematological malignancies.Copyright © 2020. Published by Elsevier Inc.
Venous hematology, biochemistry, and blood gas analysis of free-ranging Eastern Copperheads (Agkistrodon contortrix) and Eastern Ratsnakes (Pantherophis alleghaniensis).
February 17, 2020
February 17, 2020