Chronic myeloid leukemia is a malignant proliferation of the granulocytic cell line characterized by a fairly normal differentiation. The underlying genetic abnormality is the Philadelphia chromosome Philadelphia chromosome An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia. Acute Lymphoblastic Leukemia, an abbreviated chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22, resulting from reciprocal (9;22)(q34;q11) translocation. The chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics contains the BCR-ABL1 fusion gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (from ABL1 on chromosome 9 Chromosome 9 Friedreich’s Ataxia and BCR BCR Lymphocytes: Histology on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22), which induces constitutive tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase activation and consequently, uncontrolled granulocyte production. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CML can be asymptomatic or have constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis, sternal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly. Laboratory studies show an elevated WBC, and a peripheral blood smear Peripheral Blood Smear Anemia: Overview and Types shows increased numbers of immature cells. Demonstration of Philadelphia translocation using cytogenetic techniques is considered the gold standard diagnostic test. Without treatment, CML generally has a triphasic course progressing from a chronic phase Chronic phase HIV Infection and AIDS to an accelerated phase and leading to a terminal blast crisis. Management includes therapy with tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase inhibitors and palliative agents, as well as allogeneic hematopoietic cell transplantation.
Last updated: 24 Jun, 2021
Chronic myeloid leukemia is a chronic myeloproliferative neoplasm characterized by uncontrolled and dysregulated proliferation of the granulocytic lineage (mature and maturing cells), with a maintained capacity for differentiation. Chronic myeloid leukemia is also known as chronic myelocytic leukemia or chronic myelogenous leukemia.
Hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis starts with a hematopoietic stem cell, which is prompted to divide and differentiate with appropriate chemical stimuli (hemopoietic growth factors).
Bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Bones: Structure and Types marrow
hematopoiesis
Hematopoiesis
The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis).
Bone Marrow: Composition and Hematopoiesis:
Proliferation and differentiation of the formed elements of blood:
In CML, there is sustained proliferation of cells in the granulocytic line (myeloblasts →
neutrophils
Neutrophils
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Innate Immunity: Phagocytes and Antigen Presentation,
basophils
Basophils
Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes.
Innate Immunity: Phagocytes and Antigen Presentation,
eosinophils
Eosinophils
Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.
Innate Immunity: Phagocytes and Antigen Presentation). Both mature and maturing cells are seen; thus, there are cells that are only partially effective.
CFU-GEMM
CFU-GEMM
Platelets: Histology:
colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte
Colony-forming unit–granulocyte, erythrocyte, monocyte, megakaryocyte
Platelets: Histology
GM-CSF
GM-CSF
An acidic glycoprotein of mw 23 kda with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
White Myeloid Cells: Histology:
granulocyte macrophage colony-stimulating factor
Granulocyte macrophage colony-stimulating factor
An acidic glycoprotein of mw 23 kda with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
White Myeloid Cells: Histology
M-CSF
M-CSF
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a mw of 70 kda. It binds to a specific high affinity receptor.
White Myeloid Cells: Histology:
macrophage colony-stimulating factor
Macrophage colony-stimulating factor
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a mw of 70 kda. It binds to a specific high affinity receptor.
White Myeloid Cells: Histology
G-CSF:
granulocyte colony-stimulating factor
Granulocyte colony-stimulating factor
A glycoprotein of mw 25 kda containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
White Myeloid Cells: Histology
NK: natural killer
Chronic myeloid leukemia is an acquired abnormality of the hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow.
Schematic diagram of the translocation that forms the
Philadelphia chromosome
Philadelphia chromosome
An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia.
Acute Lymphoblastic Leukemia, and schematic representation of the
BCR
BCR
Lymphocytes: Histology and ABL
genes
Genes
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
DNA Types and Structure.
ABL1 and
BCR
BCR
Lymphocytes: Histology
genes
Genes
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
DNA Types and Structure reside on the long arms of
chromosomes
Chromosomes
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.
DNA Types and Structure 9 and 22, respectively. The fusion BCR-ABL
gene
Gene
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Basic Terms of Genetics is formed with the translocation of the ABL1
gene
Gene
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Basic Terms of Genetics (from
chromosome 9
Chromosome 9
Friedreich’s Ataxia) to the long
arm
Arm
The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior).
Arm: Anatomy of
chromosome
Chromosome
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.
Basic Terms of Genetics 22, creating a changed
chromosome
Chromosome
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.
Basic Terms of Genetics 22 (the so-called
Philadelphia chromosome
Philadelphia chromosome
An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia.
Acute Lymphoblastic Leukemia).
The symptoms discussed above vary in severity depending on the 3 disease phases of CML (based on the immature WBCs or blast cells in the blood or bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow).
Chronic stable phase:
Accelerated phase:
Blast crisis (or acute phase Acute phase Short Bowel Syndrome):
Bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Bones: Structure and Types marrow examination:
Blasts
Blasts
Injuries resulting when a person is struck by particles impelled with violent force from an explosion. Blast causes pulmonary contusion and hemorrhage, laceration of other thoracic and abdominal viscera, ruptured ear drums, and minor effects in the central nervous system.
Blunt Chest Trauma seen in the
bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Bones: Structure and Types marrow of a patient diagnosed with CML
FISH
FISH
A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Chromosome Testing for the detection of (9;22)(q34;q11):
In this study,
FISH
FISH
A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Chromosome Testing analysis of the ABL (9q34)
gene
Gene
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Basic Terms of Genetics was identified as fluorescent red dots and the
BCR
BCR
Lymphocytes: Histology (22q11)
gene
Gene
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Basic Terms of Genetics as green dots. Therefore, a cell exhibiting 2 separate green and red dots was considered a normal cell showing no translocation.
However, the irregular translocation in a cell was identified by 1 red and 1 green and fused red, yellow, and green signals (representing BCR-ABL
gene
Gene
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Basic Terms of Genetics fusion).
Bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Bones: Structure and Types marrow studies and
karyotyping
Karyotyping
Mapping of the karyotype of a cell.
Chromosome Testing of CML:
Bone
Bone
Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy.
Bones: Structure and Types marrow aspirates showing hypercellularity
A: x100 magnification
B: x400 magnification
C: standard
Philadelphia chromosome
Philadelphia chromosome
An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia.
Acute Lymphoblastic Leukemia (altered
chromosome
Chromosome
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.
Basic Terms of Genetics 22)
karyotype
Karyotype
The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere.
Congenital Malformations of the Female Reproductive System analysis
D: CML with more complex involvement of
chromosome
Chromosome
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell.
Basic Terms of Genetics 6
Myeloproliferative neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors can be compared with the following WHO classification:
Disease | Mutations | Key points |
---|---|---|
CML | BCR-ABL1 ( Philadelphia chromosome Philadelphia chromosome An aberrant form of human chromosome 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 percent of patients with chronic myelocytic leukemia. Acute Lymphoblastic Leukemia) | Proliferation of mature and maturing granulocytes Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the neutrophils; eosinophils; and basophils. White Myeloid Cells: Histology |
Essential thrombocythemia Essential thrombocythemia Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm characterized by the clonal thrombocytosis linked to somatic mutations involving Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL). Patients can be asymptomatic or present with vasomotor symptoms. Essential Thrombocythemia | JAK2, CALR, or MPL | Excessive clonal platelet production |
Polycythemia vera Polycythemia vera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiate PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia Vera | JAK2 | Elevated RBC mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast |
Primary myelofibrosis Primary myelofibrosis Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by chronic myeloproliferation with nonclonal fibroblastic deposition, resulting in bone marrow fibrosis. The abnormality stems from genetic mutations of the hematopoietic stem cells (typically, JAK2 mutation). Primary symptoms are anemia and extramedullary hematopoiesis,. Primary Myelofibrosis | JAK2, CALR, or MPL | Obliterative bone marrow fibrosis Bone Marrow Fibrosis Primary Myelofibrosis |
Other types:
Chronic stable phase:
Accelerated phase:
Blast crisis: