Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess
red blood cells,
white blood cells or
platelets are produced in the
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...
. ''Myelo'' refers to the
bone marrow
Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...
, ''proliferative'' describes the rapid growth of blood cells and ''
neoplasm'' describes that growth as abnormal and uncontrolled.
The overproduction of blood cells is often associated with a
somatic mutation, for example in the
JAK2,
CALR, TET2, and MPL gene markers.
In rare cases, some MPNs such as
primary myelofibrosis may accelerate and turn into
acute myeloid leukemia.
Classification
MPNs are classified as blood cancers by most institutions and organizations. In MPNs, the
neoplasm (abnormal growth) starts out as benign and can later become
malignant.
As of 2016, the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
lists the following subcategories of MPNs:
*
Chronic myeloid leukemia (CML)
*
Chronic neutrophilic leukemia (CNL)
*
Polycythemia vera (PV)
*
Primary myelofibrosis (PMF)
**
PMF, Prefibrotic Stage
**
PMF, Overt Fibrotic Stage
*
Essential thrombocythemia (ET)
*
Chronic eosinophilic leukemia (not otherwise specified)
* MPN, unclassifiable (MPN-U)
Causes
MPNs arise when
precursor cell
In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a proge ...
s (blast cells) of the
myeloid lineages in the bone marrow develop
somatic mutations which cause them to grow abnormally.
There is a similar category of disease for the lymphoid lineage, the
lymphoproliferative disorders
acute lymphoblastic leukemia,
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...
s,
chronic lymphocytic leukemia and
multiple myeloma. Genetics is believed to play a central role in the development of MPNs, specially in developing thromboembolic and bleeding complications.
Diagnosis
People with MPNs might not have symptoms when their disease is first detected via blood tests. Depending on the nature of the myeloproliferative neoplasm, 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 B
12 (or B
12 binding capacity),
serum urate
Serum may refer to:
*Serum (blood), plasma from which the clotting proteins have been removed
**Antiserum, blood serum with specific antibodies for passive immunity
*Serous fluid, any clear bodily fluid
*Truth serum, a drug that is likely to make ...
or direct sequencing of the patient's DNA.
According to WHO diagnostic criteria published in 2016, myeloproliferative neoplasms are diagnosed as follows:
* Chronic myeloid leukemia
Chronic myeloid leukemia (CML) has a presence of the hallmark
Philadelphia Chromosome
The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in Chromosome 22 (human), chromosome 22 of Leukemia, leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defe ...
(BCR-ABL1) mutation.
* Chronic neutrophilic leukemia
Chronic neutrophilic leukemia (CNL) is characterized by a mutation in the CSF3R gene and an exclusion of other causes of
neutrophilia.
* Essential thrombocythemia
Essential thrombocythemia (ET) is diagnosed with a
platelet count greater than 450 × 109/L and is associated with the
JAK2 V617F
Jak may refer to:
Places
* Ják, a village in Hungary
People
* Jak Alnwick (born 1993), English football goalkeeper
* Jak Jones (born 1993), Welsh professional snooker player
* Raymond Jackson ("JAK") (1927–1997), UK cartoonist
* Jak Airport (c ...
mutation in up to 55% of cases and with an MPL (thrombopoietin receptor) mutation in up to 5% of cases:.
There should be no increase in
reticulin fibers and the patient should not meet the criteria for other MPNs, in particular
Pre-PMF.
* Polycythemia vera
Polycythemia vera (PV) is associated most often with the JAK2 V617F mutation greater than 95% of cases, whereas the remainder has a JAK2 exon 12 mutations. High
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
or
hematocrit counts are required, as is a
bone marrow examination showing "prominent
erythroid,
granulocytic
Granulocytes are
cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They hav ...
and
megakaryocytic proliferation with pleomorphic, mature
megakaryocytes."
* Prefibrotic/early primary myelofibrosis
Prefibrotic primary myelofibrosis (Pre-PMF) is typically associated with JAK2, CALR, or MPL mutations and shows reticulin fibrosis no greater than grade 1.
Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
,
splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulati ...
,
LDH above the upper limits and
leukocytosis are minor criteria.
* Overtly fibrotic myelofibrosis
Like
pre-PMF, overt
primary myelofibrosis is associated with JAK2, CALR, or MPL mutations. However, a
bone marrow biopsy will show reticulin and/or collagen fibrosis with a grade 2 or 3.
Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
,
splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulati ...
,
LDH above the upper limits and
leukocytosis are minor criteria.
* MPN-U
Patients with otherwise unexplained thrombosis and with neoplasms can not be classified in one of the other categories.
Treatment
No curative drug treatment exists for MPNs.
Hematopoietic stem cell transplantation can be a curative treatment for a small group of patients, however MPN treatment is typically focused on symptom control and myelosuppressive drugs to help control the production of blood cells.
The goal of treatment for ET and PV is prevention of thrombohemorrhagic complications. The goal of treatment for MF is amelioration of anemia, splenomegaly, and other symptoms. Low-dose aspirin is effective in PV and ET.
Tyrosine kinase inhibitors like
imatinib have improved the prognosis of CML patients to near-normal
life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
.
Recently, a ''
JAK2'' inhibitor, namely
ruxolitinib, has been approved for use in
primary myelofibrosis.
Trials of these inhibitors are in progress for the treatment of the other myeloproliferative neoplasms.
Incidence
Although considered rare diseases, incidence rates of MPNs are increasing, in some cases tripling. It is hypothesized that the increase may be related to improved diagnostic abilities from the identification of the
JAK2 and other gene markers, as well as continued refinement of the WHO guidelines.
There is wide variation in reported MPN
incidence and
prevalence worldwide, with a
publication bias
In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance ...
suspected for
essential thrombocythemia and
primary myelofibrosis.
History
The concept of myeloproliferative disease was first proposed in 1951 by the
hematologist William Dameshek.
The discovery of the association of MPNs with the
JAK2 gene marker in 2005 and the
CALR marker in 2013 improved the ability to classify MPNs.
MPNs were classified as blood cancers by the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
in 2008. Previously, they were known as myeloproliferative diseases (MPD).
In 2016,
Mastocytosis was no longer classified as an MPN.
References
External links
*
MPN Info via Cancer.gov
{{Authority control
Myeloid neoplasia