Acute Myeloid Leukemia (AML) & Chronic Myeloid Leukemia (CML)

Leukemia originates from the bone marrow, characterized by an overflow of abnormal cells into the peripheral blood. Acute myeloid leukemia (AML) stems the rapid growth of immature granulocyte and monocyte precursors called myeloblasts in the bone marrow, AML primarily affects older adults, especially those over 65 yrs with a history of prior chemotherapy, ionizing radiation, or benzene exposure. Down syndrome also increase the risk of AML. Myeloproliferative disorders and myelodysplastic syndrome can progress into AML.

Clinically, AML presents with symptoms of functional pancytopenia such as thrombocytopenia, anemia, and functional neutropenia, which often coexists with leukocytosis from proliferating myeloblasts. Symptoms of AML include weakness, fatigue, fever, bone pain, signs of thrombocytopenia like petechiae and ecchymosis. CML is diagnosed as > 20% myeloblasts (basophilic cytoplasm, faint granules, and prominent bilobed nuclei) in bone marrow cells or peripheral WBCs. A key feature in some AML variants is the presence of Auer rods, pink structures in the myeloblast cytoplasm due to crystallization of the myeloperoxidase enzyme.

Acute promyelocytic leukemia (APL) is subtype of AML that features promyelocytes filled with Auer rods. APL occurs from a translocation between chromosomes 15 & 17, producing the PML/RARalpha fusion protein. This abnormal protein inhibits myeloid differentiation at the promyelocytic stage. A critical clinical implication of APL is the risk of disseminated intravascular coagulation (DIC) due to the release of tissue factor by promyelocytes. All-trans-retinoic acid, a Vitamin A analog, prompts the abnormal promyelocytes to mature into neutrophils and is used to treat APL.

Chronic myelogenous leukemia (CML) originates from the proliferation of mature granulocyte progenitor cells in the bone marrow and typically manifests during its chronic phase. CML is more common in the elderly and is associated with exposure to ionizing radiation. The hallmark of CML is the BCR-ABL fusion gene, which stems from a translocation merging the ABL gene from chromosome 9 with the BCR gene on chromosome 22, forming the distinctive Philadelphia chromosome. This fusion results in a continuously active receptor tyrosine kinase.

Clinically, CML presents with leukocytosis, dominated by variety of granulocytes, but with increased number of myelocytes compared to other myeloid precursors. Complications due to excessive platelets include thrombocytosis or hemorrhage from the consumption of available von Willebrand factor. Moreover, patients may develop normochromic, normocytic anemia, splenomegaly from extramedullary hematopoiesis, and even splenic infarcts. Over time, CML can transition from the chronic phase to an ‘accelerated stage,’ marked by thrombocytopenia, eventually culminating in ‘blast crisis’ from a surge in myeloblasts that mirrors the presentation of AML. Treatment predominantly involves tyrosine kinase inhibitors like imatinib, dasatinib, and nilotinib that target the kinase activity of the BCR-ABL protein.

A leukemoid reaction is a benign state characterized by a WBC exceeding 50,000—primarily neutrophils—and is often triggered by infections. Peripheral blood smear shows bands or slightly immature neutrophils, leading to a left shift in WBC distribution. Leukocyte alkaline phosphatase (LAP) can be used to differentiate CML from a leukemoid reaction, which is either normal or elevated in leukemoid reactions but reduced in CML. Additionally, during infections or inflammation, neutrophils in a leukemoid reaction may exhibit toxic granulation, Dohle bodies, & cytoplasmic vacuoles, features not typically seen in CML.