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LeukemiaLeukemia

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Leukemia Leukemia

A group of malignant disorders affecting A group of malignant disorders affecting the blood and blood-forming tissues of the blood and blood-forming tissues of – Bone marrowBone marrow– Lymph systemLymph system– SpleenSpleen

Occurs in all age groupsOccurs in all age groups

A group of malignant disorders affecting A group of malignant disorders affecting the blood and blood-forming tissues of the blood and blood-forming tissues of – Bone marrowBone marrow– Lymph systemLymph system– SpleenSpleen

Occurs in all age groupsOccurs in all age groups

:EpidemiologyCML occurs in all age groups, but most commonly in the middle-aged and elderly. Its annual incidence is 1–2 per 100,000 people, and slightly more men than women are affected. CML represents about 15–20% of all cases of adult leukemia in Western populations.The only well-described risk factor for CML is exposure to ionizing radiation; for example, increased rates of CML were seen in people exposed to the atomic bombings of Hiroshima and Nagasaki[16

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Leukemia Leukemia

Results in an accumulation of Results in an accumulation of dysfunctional cells because of a loss of dysfunctional cells because of a loss of regulation in cell divisionregulation in cell division

Fatal if untreatedFatal if untreated

– ProgressiveProgressive

Results in an accumulation of Results in an accumulation of dysfunctional cells because of a loss of dysfunctional cells because of a loss of regulation in cell divisionregulation in cell division

Fatal if untreatedFatal if untreated

– ProgressiveProgressive

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Leukemia Leukemia

Often thought of as a childhood diseaseOften thought of as a childhood disease The number of adults affected with The number of adults affected with

leukemia is 10 times that of children leukemia is 10 times that of children

Often thought of as a childhood diseaseOften thought of as a childhood disease The number of adults affected with The number of adults affected with

leukemia is 10 times that of children leukemia is 10 times that of children

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Leukemia Leukemia Etiology and PathophysiologyEtiology and Pathophysiology No single causative agent No single causative agent Most from a combination of factorsMost from a combination of factors

– Genetic and environmental influencesGenetic and environmental influences

No single causative agent No single causative agent Most from a combination of factorsMost from a combination of factors

– Genetic and environmental influencesGenetic and environmental influences

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Leukemia Leukemia Etiology and PathophysiologyEtiology and Pathophysiology Associated with the development of leukemia Associated with the development of leukemia

– Chemical agentsChemical agents

– Chemotherapeutic agentsChemotherapeutic agents

– VirusesViruses

– Radiation Radiation

– Immunologic deficiencies Immunologic deficiencies

Associated with the development of leukemia Associated with the development of leukemia

– Chemical agentsChemical agents

– Chemotherapeutic agentsChemotherapeutic agents

– VirusesViruses

– Radiation Radiation

– Immunologic deficiencies Immunologic deficiencies

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Leukemia Leukemia ClassificationClassification Acute versus chronicAcute versus chronic

– Cell maturityCell maturity• Acute:Acute:• Chronic:Chronic:

Acute versus chronicAcute versus chronic

– Cell maturityCell maturity• Acute:Acute:• Chronic:Chronic:

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Acute leukemia is characterized by a rapid increase in the number of immature blood cells there are. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children.

Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal, resulting in many abnormal white blood cells. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

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Leukemia Leukemia ClassificationClassification Type of white blood cell (WBC)Type of white blood cell (WBC)

– Acute lymphocytic leukemia (ALL)Acute lymphocytic leukemia (ALL)

– Acute myelogenous leukemia (AML)Acute myelogenous leukemia (AML)• Also called acute nonlymphoblastic Also called acute nonlymphoblastic

leukemia (ANLL)leukemia (ANLL)

– Chronic myelogenous leukemia (CML)Chronic myelogenous leukemia (CML)

– Chronic lymphocytic leukemia (CLL)Chronic lymphocytic leukemia (CLL)

Type of white blood cell (WBC)Type of white blood cell (WBC)

– Acute lymphocytic leukemia (ALL)Acute lymphocytic leukemia (ALL)

– Acute myelogenous leukemia (AML)Acute myelogenous leukemia (AML)• Also called acute nonlymphoblastic Also called acute nonlymphoblastic

leukemia (ANLL)leukemia (ANLL)

– Chronic myelogenous leukemia (CML)Chronic myelogenous leukemia (CML)

– Chronic lymphocytic leukemia (CLL)Chronic lymphocytic leukemia (CLL)

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Myelogenous Leukemia Myelogenous Leukemia

Leukemia characterized by proliferation Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in and spleen) and an abnormal increase in the number of granulocytes, myelocytes, the number of granulocytes, myelocytes, and myeloblasts in the circulating bloodand myeloblasts in the circulating blood

Leukemia characterized by proliferation Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in and spleen) and an abnormal increase in the number of granulocytes, myelocytes, the number of granulocytes, myelocytes, and myeloblasts in the circulating bloodand myeloblasts in the circulating blood

Myeloid tissue is a Myeloid tissue is a biologic tissue with the with the ability to perform ability to perform hematopoiesis. It is mainly . It is mainly found as the found as the red bone marrow in in bones, and is , and is often synonymous with this. However, myeloid often synonymous with this. However, myeloid can also be present in the can also be present in the liver and and spleen . .

A myelocyte is a young A myelocyte is a young cell of the of the granulocytic series, occurring normally in series, occurring normally in bone marrow, but , but not in circulating not in circulating blood (except when caused by (except when caused by certain diseases).certain diseases).

Myeloid tissue is a Myeloid tissue is a biologic tissue with the with the ability to perform ability to perform hematopoiesis. It is mainly . It is mainly found as the found as the red bone marrow in in bones, and is , and is often synonymous with this. However, myeloid often synonymous with this. However, myeloid can also be present in the can also be present in the liver and and spleen . .

A myelocyte is a young A myelocyte is a young cell of the of the granulocytic series, occurring normally in series, occurring normally in bone marrow, but , but not in circulating not in circulating blood (except when caused by (except when caused by certain diseases).certain diseases).

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Granulocytes are a category of Granulocytes are a category of white blood cells characterized by the characterized by the presence of presence of granules in their in their cytoplasm..[1] They are also called polymorphonuclear They are also called polymorphonuclear leukocytes (PMN or PML) because of the leukocytes (PMN or PML) because of the varying shapes of the varying shapes of the nucleus, which is , which is usually lobed into three segments.usually lobed into three segments.

The myeloblast is a unipotent stem cell, The myeloblast is a unipotent stem cell, which will differentiate into one of the which will differentiate into one of the actors of the actors of the granular series. series.

Granulocytes are a category of Granulocytes are a category of white blood cells characterized by the characterized by the presence of presence of granules in their in their cytoplasm..[1] They are also called polymorphonuclear They are also called polymorphonuclear leukocytes (PMN or PML) because of the leukocytes (PMN or PML) because of the varying shapes of the varying shapes of the nucleus, which is , which is usually lobed into three segments.usually lobed into three segments.

The myeloblast is a unipotent stem cell, The myeloblast is a unipotent stem cell, which will differentiate into one of the which will differentiate into one of the actors of the actors of the granular series. series.8/12/20098/12/2009 1313

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Acute Myelogenous Leukemia Acute Myelogenous Leukemia (AML)(AML) Leukemia characterized by proliferation of myeloid Leukemia characterized by proliferation of myeloid

tissue (as of the bone marrow and spleen) and an tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating bloodmyelocytes, and myeloblasts in the circulating blood

One fourth of all leukemiasOne fourth of all leukemias– 85% of the acute leukemias in adults85% of the acute leukemias in adults

Abrupt, dramatic onsetAbrupt, dramatic onset– Serious infections, abnormal bleedingSerious infections, abnormal bleeding

Uncontrolled proliferation of myeloblastsUncontrolled proliferation of myeloblasts– Hyperplasia of bone marrow and spleenHyperplasia of bone marrow and spleen

Leukemia characterized by proliferation of myeloid Leukemia characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating bloodmyelocytes, and myeloblasts in the circulating blood

One fourth of all leukemiasOne fourth of all leukemias– 85% of the acute leukemias in adults85% of the acute leukemias in adults

Abrupt, dramatic onsetAbrupt, dramatic onset– Serious infections, abnormal bleedingSerious infections, abnormal bleeding

Uncontrolled proliferation of myeloblastsUncontrolled proliferation of myeloblasts– Hyperplasia of bone marrow and spleenHyperplasia of bone marrow and spleen

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Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia (CML)(CML) Excessive development of mature Excessive development of mature

neoplastic granulocytes in the bone neoplastic granulocytes in the bone marrowmarrow

– Move into the peripheral blood in Move into the peripheral blood in massive numbersmassive numbers

– Ultimately infiltrate the liver and Ultimately infiltrate the liver and spleen spleen

Excessive development of mature Excessive development of mature neoplastic granulocytes in the bone neoplastic granulocytes in the bone marrowmarrow

– Move into the peripheral blood in Move into the peripheral blood in massive numbersmassive numbers

– Ultimately infiltrate the liver and Ultimately infiltrate the liver and spleen spleen

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Chronic Myelogenous LeukemiaChronic Myelogenous Leukemia

Philadelphia chromosomePhiladelphia chromosome

– The The chromosome abnormality that abnormality that causes causes chronic myeloid leukemia leukemia (CML) (9 &22)(CML) (9 &22)

– Genetic markerGenetic marker Chronic, stable phase followed by acute, Chronic, stable phase followed by acute,

aggressive (blastic) phaseaggressive (blastic) phase

Philadelphia chromosomePhiladelphia chromosome

– The The chromosome abnormality that abnormality that causes causes chronic myeloid leukemia leukemia (CML) (9 &22)(CML) (9 &22)

– Genetic markerGenetic marker Chronic, stable phase followed by acute, Chronic, stable phase followed by acute,

aggressive (blastic) phaseaggressive (blastic) phase

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Leukemia Leukemia Clinical ManifestationsClinical Manifestations Relate to problems caused byRelate to problems caused by

– Bone marrow failureBone marrow failure• Overcrowding by abnormal cellsOvercrowding by abnormal cells• Inadequate production of normal marrow Inadequate production of normal marrow

elementselements• Anemia, thrombocytopenia, Anemia, thrombocytopenia, ↓ number ↓ number

and function of WBCsand function of WBCs

Relate to problems caused byRelate to problems caused by

– Bone marrow failureBone marrow failure• Overcrowding by abnormal cellsOvercrowding by abnormal cells• Inadequate production of normal marrow Inadequate production of normal marrow

elementselements• Anemia, thrombocytopenia, Anemia, thrombocytopenia, ↓ number ↓ number

and function of WBCsand function of WBCs

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Leukemia Leukemia Clinical ManifestationsClinical Manifestations Relate to problems caused byRelate to problems caused by

– Leukemic cells infiltrate patient’s Leukemic cells infiltrate patient’s organsorgans• SplenomegalySplenomegaly• HepatomegalyHepatomegaly• LymphadenopathyLymphadenopathy• Bone pain, meningeal irritation, oral Bone pain, meningeal irritation, oral

lesions (chloromas)lesions (chloromas)

Relate to problems caused byRelate to problems caused by– Leukemic cells infiltrate patient’s Leukemic cells infiltrate patient’s

organsorgans• SplenomegalySplenomegaly• HepatomegalyHepatomegaly• LymphadenopathyLymphadenopathy• Bone pain, meningeal irritation, oral Bone pain, meningeal irritation, oral

lesions (chloromas)lesions (chloromas)

It is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome

CML was the first malignancy to be linked to a clear genetic abnormality, the chromosomal translocation known as the Philadelphia chromosome. This chromosomal abnormality is so named because it was first discovered and described in 1960 by two scientists from Philadelphia,Pennsylvania:

This exchange brings together two genes: the BCR (breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia virus) on chromosome 9. The resulting hybrid gene BCR-ABL codes for a fusion protein with tyrosine kinase activity, which activates signal transduction pathways, leading to uncontrolled cell growth.

The Philadelphia chromosome:

T (9:22) translocationT (9:22) translocation..The Ph chromosome is a shortened The Ph chromosome is a shortened

chromosome 22, which result from Reciprocal chromosome 22, which result from Reciprocal translocation between the long arms of translocation between the long arms of chromosomes 9 & 22 ,The result is a hybrid chromosomes 9 & 22 ,The result is a hybrid bcr-abl gene (fusion protein) with increased bcr-abl gene (fusion protein) with increased tyrosine Kinase acm resulting in leukemic tyrosine Kinase acm resulting in leukemic transformationtransformation..