What is myeloid shift?

Myeloid Shift: Definition and Clinical Significance

Myeloid shift refers to the presence of increased immature myeloid cells in peripheral blood, characterized by a "left shift" in the maturation spectrum of granulocytes, indicating an emergency response to infection, inflammation, or other pathological conditions. This hematological finding is clinically significant as it may indicate underlying disease processes that require prompt evaluation and management.

Characteristics of Myeloid Shift

• Definition: A myeloid shift (or "left shift") is characterized by the presence of immature granulocytic cells in peripheral blood, including:

  • Metamyelocytes
  • Myelocytes
  • Promyelocytes
  • Band forms (immature neutrophils)

• Quantitative criteria: Typically defined as ≥1% of metamyelocytes, myelocytes, or promyelocytes in peripheral blood 1

• Pathophysiology: Represents an emergency myelopoiesis response where immature cells are released prematurely from bone marrow to combat threats such as:

  • Infections
  • Inflammation
  • Tissue damage
  • Malignancy

Clinical Contexts of Myeloid Shift

Normal vs. Pathological Myelopoiesis

• Normal myelopoiesis: A structured process where common precursors acquire specific markers and functions while progressively losing self-renewal capacity 2

• Pathological myelopoiesis: Occurs when various conditions perturb the steady supply of leukocytes, resulting in emergency myelopoiesis with premature release of immature forms 2

Associated Conditions

1. Reactive causes (most common):

   • Acute bacterial infections
   • Severe inflammation
   • Tissue injury/trauma
   • Post-surgical states

2. Hematologic malignancies:

   • Chronic myeloid leukemia (CML)
   • Myeloproliferative disorders
   • Myelodysplastic syndromes (MDS)

3. Other pathological conditions:

   • Severe hemorrhage
   • Hemolysis
   • Drug reactions
   • Toxin exposure

Diagnostic Evaluation

When myeloid shift is identified, the following evaluations are recommended:

• Complete blood count with differential: To assess hemoglobin, platelet count, and proportions of different white cell types 3

• Peripheral blood smear examination: To identify:

  • Specific immature myeloid forms
  • Dysplastic features
  • Other morphological abnormalities 3

• Bone marrow examination: Indicated when suspecting underlying hematologic malignancy to assess:

  • Cellularity
  • Dysplasia
  • Blast percentage
  • Fibrosis 3

• Cytogenetic analysis: Essential for detecting clonal chromosomal abnormalities when malignancy is suspected 3

Clinical Significance

• Prognostic indicator: In acute lymphocytic leukemia, the presence of left shift at diagnosis correlates with longer complete remission duration (74% vs 42% at 92 months) 1

• Disease monitoring: Changes in the degree of myeloid shift can indicate response to treatment or disease progression

• Diagnostic clue: May help differentiate between:

  • Reactive processes vs. hematologic malignancies
  • Different types of myeloid neoplasms
  • CML blast phase vs. Philadelphia chromosome-positive acute lymphoblastic leukemia 2

Important Distinctions

Myeloid Shift vs. Myeloid-Derived Suppressor Cells (MDSCs)

• Myeloid shift: Refers to the presence of immature myeloid cells in peripheral blood as part of emergency myelopoiesis

• MDSCs: Specific immature myeloid cells with immunosuppressive functions that accumulate during chronic inflammation, cancer, and autoimmune diseases 2

  • Include polymorphonuclear (PMN) and monocytic (M) subtypes
  • Characterized by specific immunophenotypic markers (CD11b+, Gr-1+)
  • Play important roles in immune regulation and tumor-dependent immune dysfunction

Myeloid Shift vs. Myelodysplasia

• Myeloid shift: Primarily quantitative change in myeloid maturation with normal morphology

• Myelodysplasia: Qualitative abnormalities in cell morphology including:

  • Abnormal cytoplasmic maturation (pale basophilic cytoplasm)
  • Abnormal nuclear maturation (open chromatin)
  • Abnormal nuclear shape (lobated vs. ring-shaped nuclei) 2

Clinical Approach to Myeloid Shift

1. Determine if reactive or neoplastic:

   • Assess for signs/symptoms of infection or inflammation
   • Review medication history
   • Evaluate for signs of underlying malignancy

2. If suspected neoplastic process:

   • Perform bone marrow examination
   • Conduct cytogenetic and molecular testing
   • Consider flow cytometry for immunophenotyping

3. Monitor for progression:

   • Serial blood counts
   • Reassessment of clinical status
   • Response to therapeutic interventions

Pitfalls and Caveats

• Misinterpretation: Left shift can be misinterpreted as leukemia or missed entirely if not specifically evaluated in the differential count

• Transient nature: Reactive myeloid shifts may resolve quickly with treatment of underlying cause

• Concurrent conditions: Multiple conditions can cause myeloid shift simultaneously, complicating interpretation

• Therapy effects: Certain medications (e.g., corticosteroids, growth factors) can induce myeloid shifts independent of underlying disease