Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

white blood cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

s or

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

s 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

, ''proliferative'' describes the rapid growth of blood cells and ''

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

'' describes that growth as abnormal and uncontrolled. The overproduction of blood cells is often associated with a

somatic mutation A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline m ...

, 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 Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with haematopoiesis, normal blood cell production. Sympto ...

Classification

MPNs are classified as blood cancers by most institutions and organizations. In MPNs, the

(abnormal growth) starts out as benign and can later become

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

. 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 Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulat ...

(CML) * Chronic neutrophilic leukemia (CNL) *

Polycythemia vera Polycythemia vera is an uncommon myeloproliferative neoplasm (a type of chronic leukemia) in which the bone marrow makes too many red blood cells. It may also result in the overproduction of white blood cells and platelets. Most of the health ...

(PV) * Primary myelofibrosis (PMF) ** PMF, Prefibrotic Stage ** PMF, Overt Fibrotic Stage *

Essential thrombocythemia Essential thrombocythemia (ET) is a rare chronic blood cancer (myeloproliferative neoplasm) characterised by the overproduction of platelets (thrombocytes) by megakaryocytes in the bone marrow. It may, albeit rarely, develop into acute myeloid le ...

(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 ...

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, n ...

and

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, ane ...

. 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 Oxygen saturation (symbol SO2) is a relative measure of the concentration of oxygen that is dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium at the given temperature. It ca ...

and carboxyhaemoglobin level, neutrophil alkaline phosphatase level, vitamin B₁₂ (or B₁₂ binding capacity), serum urate 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

(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

(ET) is diagnosed with a

count greater than 450 × 109/L and is associated with the JAK2 V617F 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 Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a support ...

fibers and the patient should not meet the criteria for other MPNs, in particular Pre-PMF. * 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 ...

hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is nor ...

counts are required, as is a bone marrow examination showing "prominent erythroid, granulocytic and

megakaryocytic A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In h ...

proliferation with pleomorphic, mature

megakaryocyte A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In h ...

s." * 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 Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a s