Steps in the Diagnosis of Chronic Myeloid Leukemia

Left-shift leukocytosis in conjunction with usually low-grade anemia, thrombocytopenia or thrombocytosis (which often correlates with the migration of small megakaryocyte nuclei into the blood stream), and clinical splenomegaly is typical of CML. LDH and uric acid concentrations are elevated as a result of the increased cell turnover.

The average "typical" cell composition is as follows (in a series analyzed by Spiers): about 2% myeloblasts, 3% promyelocytes, 24% myelocytes, 8% metamyelocytes, 57% band and segmented neutrophilic granulocytes, 3% basophils, 2% eosinophils, 3% lymphocytes, and 1 % monocytes.

In almost all cases of CML the hematopoietic cells display a marker chromosome, an anomalously configured chromosome 22 (Philadelphia chromosome). The translocation responsible for the Philadelphia chromosome corresponds to a special fusion gene (BCR-ABL) that can be determined by polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH).

Left shift as far as myeloblasts, proliferation of eosinophils and basophils suggest chronic myeloid leukemia (CML)

Cml Myelocyte

Fig. 39 CML. a Blood analysis in chronic myeloid leukemia (chronic phase): segmented neutrophilic granulocytes (1), band granulocyte (2) (looks like a metamyelocyte after turning and folding of the nucleus), myelocyte with defective granulation (3), and promyelocyte (4). b and c Also chronic phase: myeloblast (1), promyelocyte (2), myelocyte with defective granulation (3), immature eosinophil (4), and basophil (5) (the granules are larger and darker, the nuclear chromatin denser than in a promyelocyte).

Fig. 39 CML. a Blood analysis in chronic myeloid leukemia (chronic phase): segmented neutrophilic granulocytes (1), band granulocyte (2) (looks like a metamyelocyte after turning and folding of the nucleus), myelocyte with defective granulation (3), and promyelocyte (4). b and c Also chronic phase: myeloblast (1), promyelocyte (2), myelocyte with defective granulation (3), immature eosinophil (4), and basophil (5) (the granules are larger and darker, the nuclear chromatin denser than in a promyelocyte).

Bone Marrow Analysis in CML. In many clinical situations, the findings from the CBC, the BCR-ABL transformation and the enlarged spleen unequivocally point to a diagnosis of CML. Analysis of the bone marrow should be performed because it provides a series of insights into the disease processes.

Normally, the cell density is considerably elevated and granulopoietic cells predominate in the CBC. Cells in this series mature properly, apart from a slight left shift in the chronic phase of CML. CML differs from reactive leukocytoses because there are no signs of stress, such as toxic granulation or dissociation in the nuclear maturation process.

Mature neutrophils may occasionally show pseudo-Pelger forms (p. 43) and the eosinophilic and, especially, basophilic granulocyte counts are often elevated. The proportion of cells from the red blood cell series decreases. Histiocytes may store glucocerebrosides, as in Gaucher syndrome (pseudo-Gaucher cells), or lipids in the form of sea-blue precipitates (sea-blue histiocytes after Romanowsky staining).

Megakaryocytes are usually increased and are often present as micro-megakaryocytes, with one or two nuclei which are only slightly larger than those of promyelocytes. Their cytoplasm typically shows clouds of granules, as in the maturation of thrombocytes.

Bone marrow analysis is not obligatory in chronic myeloid leukemia, but helps to distinguish between the various chronic myeloproliferative disorders a b

Cloud Like Megakaryocyte

Fig. 40 Bone marrow cytology in CML. a Bone marrow cytology in the chronic phase: increased cell density due to increased, left-shifted granulopoiesis, e.g., promyelocyte nest (1) and megakaryopoiesis (2). Eosinophils are increased (arrows), erythropoiesis reduced. b Often micromegakaryocytes are found in the bone marrow cytology. c Pseudo-Gaucher cells in the bone marrow in CML.

Fig. 40 Bone marrow cytology in CML. a Bone marrow cytology in the chronic phase: increased cell density due to increased, left-shifted granulopoiesis, e.g., promyelocyte nest (1) and megakaryopoiesis (2). Eosinophils are increased (arrows), erythropoiesis reduced. b Often micromegakaryocytes are found in the bone marrow cytology. c Pseudo-Gaucher cells in the bone marrow in CML.

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Responses

  • Paciano
    What is a left shift in hematology?
    8 years ago
  • jonas
    What is typical metamyeloctye in diagnosing cml?
    7 years ago
  • Sally
    What is left shifted granulopoiesis?
    6 years ago

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