🩸 👩🏼‍🔬What is CHIP in Hematology?

• ⚠️CHIP is an abbreviation for Clonal Hematopoiesis of Indeterminate Potential, and it corresponds to the presence of clonal molecular genetic or cytogenetic changes in blood or bone marrow cells.
  

• These changes are specific to the distinct subpopulation of myeloid cells that have acquired (somatic) mutations and germline mutations that have an important role in CHIP development.
  

• An important note is that CHIP is not malignant. Still, the term indeterminate in the name Clonal Hematopoiesis of Indeterminate Potential indicates the uncertainty of its potential and future potential transformation [citation].

• In 2015, a formal definition of clonal hematopoiesis of indeterminate potential (CHIP) was proposed with the following qualifiers:

  • 1️⃣ CHIP must occur in the absence of morphological variation in blood cells

  • 2️⃣ a candidate driver gene mutation should be present at a variant allele frequency of at least 2% in peripheral blood and

  • 3️⃣ in the absence of diagnostic criteria for hematologic malignancy.
    

• In ~80% of patients with Clonal Hematopoiesis of Indeterminate Potential (CHIP) have mutations in:

  • DNMT3A, TET2, and ASXL1, known as epigenetic regulators

  • PPM1D, TP53, known as DNA damage repair genes

  • JAK2, known as a gene encoding regulatory tyrosine kinase (more about this gene in this blog post here) or

  • SF3B1 and SRSF2, known as mRNA spliceosome components
    

• DNMT3A, TET2, and ASXL1 mutations are also found in AML, hematological malignancy, and other diseases, so CHIP has a potential prognostic value for such medical events.