The
myeloproliferative diseases ("MPD"s) are a group of diseases of the
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
in which excess cells are produced. They are related to, and may evolve into,
myelodysplastic syndromeThe myelodysplastic syndromes are a diverse collection of hematological conditions united by ineffective production of myeloid blood cells and risk of transformation to acute myelogenous leukemia . MDS has been found in humans, cats and dogs. Anemia requiring chronic blood transfusion is...
and
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the eminent hematologist
William DameshekWilliam Dameshek was an American hematologist. Trained at Harvard, he was the founder of Blood, the prime core clinical journal of hematology, in 1946. He is also credited with describing the concept of myeloproliferative diseases in 1951...
. In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms".
The
myeloproliferative diseases ("MPD"s) are a group of diseases of the
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
in which excess cells are produced. They are related to, and may evolve into,
myelodysplastic syndromeThe myelodysplastic syndromes are a diverse collection of hematological conditions united by ineffective production of myeloid blood cells and risk of transformation to acute myelogenous leukemia . MDS has been found in humans, cats and dogs. Anemia requiring chronic blood transfusion is...
and
acute myeloid leukemiaAcute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the eminent hematologist
William DameshekWilliam Dameshek was an American hematologist. Trained at Harvard, he was the founder of Blood, the prime core clinical journal of hematology, in 1946. He is also credited with describing the concept of myeloproliferative diseases in 1951...
. In the most recent World Health Organization classification of Hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.
Classification
Although not a
malignant neoplasmCancer is a class of diseases in which a group of cells display uncontrolled growth , invasion , and sometimes metastasis...
like other cancers, MPDs are classified within the
hematological neoplasmsHematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
.
There are four main myeloproliferative diseases, which can be further categorized by the presence of the
Philadelphia chromosomePhiladelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
:
| Philadelphia Chromosome "positive" |
Philadelphia Chromosome "negative" |
- Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...
(CML) |
Polycythemia vera Polycythemia vera is a blood disorder in which the bone marrow makes too many red blood cells. Polycythemia vera may also result in the overproduction of white blood cells and platelets...
(PV)
Essential thrombocytosisEssential thrombocytosis is a rare chronic blood disorder characterized by the overproduction of platelets by megakaryocytes in the bone marrow in the absence of an alternative cause. In some cases this disorder may be progressive, and rarely may evolve into acute myeloid leukemia or myelofibrosis...
(ET)
MyelofibrosisMyelofibrosis, also known as myeloid metaplasia, chronic idiopathic myelofibrosis, and primary myelofibrosis, is a disorder of the bone marrow...
(MF) |
In 2001, the
World Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health...
classified "
chronic eosinophilic leukemiaChronic eosinophilic leukemia is a disease in which too many eosinophils are found in the bone marrow, blood, and other tissues. Chronic eosinophilic leukemia may stay the same for many years, or it may progress quickly to acute leukemia.- External links :* entry in the public domain NCI...
/
hypereosinophilic syndromeThe hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.HS is a diagnosis of exclusion, after clonal eosinophilia...
" and
chronic neutrophilic leukemiaChronic neutrophilic leukemia is a rare myeloproliferative disorder that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.-Epidemiology:This is a rare disease,...
under "Chronic myeloproliferative diseases".
Causes
All MPDs arise from precursors of the "
myeloidThe term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
" lineage in the bone marrow. The lymphoid lineage may produce similar diseases, the lymphoproliferative disorders (
acute lymphoblastic leukemiaAcute lymphoblastic leukemia , is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone...
,
lymphomaLymphoma is a cancer that begins in the lymphocytes of the immune system and presents as a solid tumor of lymphoid cells. They often originate like balls in lymph nodes, presenting as an enlargement of the node...
s,
chronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are abnormal and malignant neoplastic proliferations of the white blood cells . CLL involves a particular subtype of white blood cells, which is a lymphocyte called a B...
and
multiple myelomaMultiple myeloma , also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease is a cancer of the white blood cells known as plasma cells. A type of B cell, plasma cells are a crucial part of the immune system responsible for the production of antibodies in humans and other vertebrates...
).
Diagnosis
Depending on the nature of the myeloproliferative disorder, diagnostic tests may include red cell mass determination (for polycythemia), bone marrow aspirate and trephine biopsy, arterial oxygen saturation and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B12 (or B12 binding capacity) and serum urate.
According to the WHO Classification of Hematopoietic and Lymphoid Neoplasms 2008 myeloproliferative disorders are divided into the following by diagnostic characteristics:
1. Chronic myelogenous leukemia (CML) with defining translocation t(9;22) BCR-ABL translocation which has three breakpoints:
a. u-BCR-ABL (p230): leads to CML with usual neutrophilia and basophilia.
b. minor-BCR-ABL (p190): leads to CML which has a tendency to become acute lymphoblastic leukemia (ALL) usually precursor B ALL and rarely precursor T ALL.
c. major-BCR-ABL (p210): normal usual breakpoint
2. Primary myelofibrosis associated with JAK2 mutation in up to 50% of cases and MPL (thrombopoietin receptor) mutation in up to 5% of cases
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome (collagenous) fibrosis, and increased myeloid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
3. Polycythemia vera associated most often with JAK2 mutation in up to 80% of cases
a. Cellular phase - increased megakaryocytes which cluster, reticulin fibrosis, later trichrome fibrosis, and increased myeloid and erythroid precursors
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
4. Essential Thrombocythemia associated with JAK2 mutation in up to 20% of cases and MPL (thrombopoietin receptor) mutation in up to 15% of cases
a. Cellular phase - increased large megakaryocytes with fibrosis and little increase in other bone marrow elements
b. Fibrotic phase - collagenous fibrosis with lack of marrow elements
These disorders are still being revised according to more specific genetic mutations and how often patients end in a fibrotic marrow event.
In 2005, the discovery of the JAK2 V617F mutation provided some evidence to suggest a common pathogenesis for the Philadelphia Chromosome negative MPDs.
External links