Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:

In 2008, the World Health Organization listed these diagnoses as types of MPD:

- Chronic myelogenous leukemia (BCR-ABL1–positive)

- Chronic neutrophilic leukemia

- Polycythemia vera

- Primary myelofibrosis

- Essential thrombocythemia

- Chronic eosinophilic leukemia (not otherwise specified)

- Mastocytosis

The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, 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 hematologist William Dameshek. 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.

The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.

The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood). Most of these conditions are common, nonspecific signs and symptoms.

Children with JMML and neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):

- 6 or more café-au-lait (flat, coffee-colored) spots on the skin

- 2 or more neurofibromas (pea-size bumps that are noncancerous tumors) on or under the skin

- Plexiform neurofibromas (larger areas on skin that appear swollen)

- Optic glioma (a tumor on the optic nerve that affects vision)

- Freckles under the arms or in the groin

- 2 or more Lisch nodules (tiny tan or brown-colored spots on the iris of the eye)

- Various bone deformations including bowing of the legs below the knee, scoliosis, or thinning of the shin bone

Noonan syndrome (NS) may predispose to the development of JMML or a myeloproliferative disorder (MPD) associated with NS (MPD/NS) which resembles JMML in the first weeks of life. However, MPD/NS may resolve without treatment. Children with JMML and Noonan's syndrome may also exhibit any of the following most-common symptoms associated with Noonan's syndrome:

- Congenital heart defects, in particular, pulmonic stenosis (a narrowing of the valve from the heart to the lungs)

- Undescended testicles in males

- Excess skin and low hair line on back of neck

- Widely set eyes

- Diamond-shaped eyebrows

- Ears that are low-set, backward-rotated, thick outer rim

- Deeply grooved philtrum (upper lip line)

- Learning delays

Most signs and symptoms of AML are caused by the replacement of normal blood cells with leukemic cells. A lack of normal white blood cell production makes people more susceptible to infections; while the leukemic cells themselves are derived from white blood cell precursors, they have no infection-fighting capacity. A drop in red blood cell count (anemia) can cause fatigue, paleness, and shortness of breath. A lack of platelets can lead to easy bruising or bleeding with minor trauma.

The early signs of AML are often vague and nonspecific, and may be similar to those of influenza or other common illnesses. Some generalized symptoms include fever, fatigue, weight loss or loss of appetite, shortness of breath, anemia, easy bruising or bleeding, petechiae (flat, pin-head sized spots under the skin caused by bleeding), bone and joint pain, and persistent or frequent infections.

Enlargement of the spleen may occur in AML, but it is typically mild and asymptomatic. Lymph node swelling is rare in AML, in contrast to acute lymphoblastic leukemia. The skin is involved about 10% of the time in the form of leukemia cutis. Rarely, Sweet's syndrome, a paraneoplastic inflammation of the skin, can occur with AML.

Some people with AML may experience swelling of the gums because of infiltration of leukemic cells into the gum tissue. Rarely, the first sign of leukemia may be the development of a solid leukemic mass or tumor outside of the bone marrow, called a chloroma. Occasionally, a person may show no symptoms, and the leukemia may be discovered incidentally during a routine blood test.

One of the most common signs of CMML is splenomegaly, found in approximately half of cases. Other less frequent signs and symptoms consist of anaemia, fever, weight loss, night sweats, infection, bleeding, synovitis, lymphadenopathy, skin rashes, pleural effusion, pericardial effusion and peritoneal effusion.

The most common symptoms of AEL are related to pancytopenia (a shortage of all types of blood cells), including fatigue, infections, and mucocutaneous bleeding. Almost half of people with AEL exhibit weight loss, fever and night sweats at the time of diagnosis. Almost all people with AEL are anemic, and 77% have a hemoglobin level under 10.0 g/dl. Signs of thrombocytopenia are found in about half of people with AEL.

The way CML presents depends on the stage of the disease at diagnosis as it has been known to skip stages in some cases.

Most patients (~90%) are diagnosed during the chronic stage which is most often asymptomatic. In these cases it may be diagnosed incidentally with an elevated white blood cell count on a routine laboratory test. It can also present with symptoms indicative of hepatosplenomegaly and the resulting upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.

Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.

Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis.

Signs and symptoms are nonspecific and generally related to the blood cytopenias:

- Anemia (low RBC count or reduced hemoglobin) —chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain

- Neutropenia (low neutrophil count) — increased susceptibility to infection

- Thrombocytopenia (low platelet count) — increased susceptibility to bleeding and ecchymosis (bruising), as well as subcutaneous hemorrhaging resulting in purpura or petechiae

Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:

- Neutropenia, anemia, and thrombocytopenia

- Splenomegaly or rarely hepatomegaly

- Abnormal granules in cells, abnormal nuclear shape and size

- Chromosome abnormality, including chromosomal translocations and abnormal chromosome number

Although some risk exists for developing acute myelogenous leukemia, about 50% of deaths occur as a result of bleeding or infection. However, leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment.

Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea, and pallor, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important fact in the person's medical history. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process.

The primary sign of myelofibrosis is reactive bone marrow fibrosis, but it is often accompanied by:

- Abdominal fullness related to an enlarged spleen (splenomegaly).

- Bone pain

- Bruising and easy bleeding due to inadequate numbers of platelets

- Cachexia (loss of appetite, weight loss, and fatigue)

- Enlargement of both the liver and spleen

- Fatigue

- Gout and high uric acid levels

- Increased susceptibility to infection, such as pneumonia

- Pallor and shortness of breath due to anemia

- In rarer cases, a raised red blood cell volume

- Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.

Myelofibrosis, also known as osteomyelofibrosis, is a relatively rare bone marrow cancer. It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.

The term "myelofibrosis" alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (cIMF); the terms idiopathic and primary mean that in these cases the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously. The terms agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) are also used to refer to primary myelofibrosis.

Acute erythroid leukemia or Di Guglielmo syndrome is a rare form of acute myeloid leukemia (less than 5% of AML cases) where the myeloproliferation is of erythroblastic precursors. It is defined as type "M6" under the FAB classification.

Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. Early on there are typically no symptoms. Later symptoms may include feeling tired, shortness of breath, easy bleeding, or frequent infections. Some types may develop into acute myeloid leukemia.

Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow.

Treatments may include supportive care, drug therapy, and stem cell transplantation. Supportive care may include blood transfusions, medications to increase the making of red blood cells, and antibiotics. Drug therapy may include the medication lenalidomide, antithymocyte globulin, and azacitidine. Certain people can be cured with chemotherapy followed by a stem-cell transplant from a donor.

About seven per 100,000 people are affected with about four per 100,000 people newly acquiring the condition each year. The typical age of onset is 70 years. The outlook depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the chromosomes of the affected cells. The typical survival rate following diagnosis is 2.5 years. The conditions were first recognized in the early 1900s. The current name came into use in 1976.

Very rarely, chloroma can occur without a known pre-existing or concomitant diagnosis of acute leukemia, acute promyleocytic leukemia or MDS/MPS; this is known as primary chloroma. Diagnosis is particularly challenging in this situation (see below). In almost all reported cases of primary chloroma, acute leukemia has developed shortly afterward (median time to development of acute leukemia 7 months, range 1–25 months). Therefore, primary chloroma could be considered an initial manifestation of acute leukemia, rather than a localized process, and could be treated as such. Where disease development or markers indicate progresses to acute promyleocytic leukemia (AML3) treatment should be tailored to this form of disease.

Chronic myelomonocytic leukaemia (CMML) is a type of leukaemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell.

CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative disorder (MPD); a disorder characterised by the overproduction of blood cells. For this reason CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organisation (WHO) states that the blood monocyte count must be >1x10/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be <20% and dysplasia of at least one lineage of myeloid blood cell should be present.

Azacitidine is a drug used to treat CMML and is approved by the Food and Drug Administration (FDA) and the European Medicines Agency. Stem cell transplant is also used to treat CMML, and involves the transplantation of donor haematopoietic stem cells into the recipient. Blood transfusion and erythropoietin are used to treat disease associated anaemia.

About 90% of JMML patients have some sort of genetic abnormality in their leukemia cells that can be identified with laboratory testing. This includes:

- 15-20% of patients with neurofibromatosis 1 (NF1)

- 25% of patients with mutations in one of the RAS family of oncogenes (only in their leukemia cells)

- Another 35% of patients with a mutation in a gene called PTPN11 (again, only in their leukemia cells).

Chloromas may occur in virtually any organ or tissue. The most common areas of involvement are the skin (also known as "leukemia cutis") and the gums. Skin involvement typically appears as violaceous, raised, nontender plaques or nodules, which on biopsy are found to be infiltrated with myeloblasts

Other tissues which can be involved include lymph nodes, the small intestine, the mediastinum, the lung, epidural sites, the uterus, the ovaries, and the orbit of the eye. Symptoms of chloroma at these sites are related to their anatomic location; chloromas may also be asymptomatic and be discovered incidentally in the course of evaluation of a person with acute myeloid leukemia.

Central nervous system involvement, as described above, most often takes the form of "meningeal leukemia", or invasion of the subarachnoid space by leukemic cells. This condition is usually considered separately from chloroma, as it requires different treatment modalities. True chloromas (i.e. solid leukemic tumors) of the central nervous system are exceedingly rare, but has been described.

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 normal blood cells. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly and is typically fatal within weeks or months if left untreated.

Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes; for which treatments and outcomes may vary.

AML is typically initially treated with chemotherapy aimed at inducing remission. People may than go on to receive additional chemotherapy, radiation therapy, or a stem cell transplant. The specific genetic mutations present within the cancer cells may guide therapy, as well as determine how long that person is likely to survive. Arsenic trioxide may be tried in cases that have recurred following usual treatments.

AML affected about one million people globally in 2015 and resulted in 147,000 deaths. It most commonly occurs in older adults. Males are affected more often than females. AML is curable in about 35% of people under 60 years old and 10% over 60 years old. Older people who are not healthy enough to receive intensive chemotherapy have a typical survival of 5–10 months. It accounts for roughly 1.8% of cancer deaths in the United States.

Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. During this phase, patients are usually asymptomatic or have only mild symptoms of fatigue, left side pain, joint and/or hip pain, or abdominal fullness. The duration of chronic phase is variable and depends on how early the disease was diagnosed as well as the therapies used. In the absence of treatment, the disease progresses to an accelerated phase. Precise patient staging based on clinical markers and personal genomic profile will likely prove beneficial in the assessment of disease history with respect to progression risk.

Atypical chronic myeloid leukemia (aCML) is a type of leukemia. It is a heterogeneous disorder belonging to the group of myelodysplastic/myeloproliferative (MDS/MPN) syndromes.

In aCML many clinical features (splenomegaly, myeloid predominance in the bone marrow with some dysplastic features but without a differentiation block) and laboratory abnormalities (myeloid proliferation, low leukocyte alkaline phosphatase values) suggest the diagnosis of chronic myelogenous leukemia (CML). However the lack of the pathognomonic Philadelphia chromosome and of the resulting BCR-ABL1 fusion point to a different pathogenetic process. Since no specific recurrent genomic or karyotypic abnormalities have been identified in aCML, the molecular pathogenesis of this disease has remained elusive and the outcome dismal (median survival 37 months) with no improvement over the last 20 years. This sharply contrasts with the outcome for CML, for which the prognosis was dramatically improved by the development of imatinib as a specific inhibitor of the BCR-ABL protein and in particular for CML.

In 2012 "SETBP1" was identified as a novel oncogene in aCML; specific somatic mutations of this gene were discovered in people with aCML and related diseases. These mutations, which are identical to the ones present in SGS as germline mutations, impair the degradation of SETBP1 and therefore cause increased cellular levels of the protein.

Acute myelomonocytic leukemia (AMMoL) is a form of acute myeloid leukemia that involves a proliferation of CFU-GM myeloblasts and monoblasts.

It is classified under "M4" in the French-American-British classification (FAB).

It is classified under "AML, not otherwise classified" in the WHO classification.

Translocations have been observed.

Progression from myelodysplastic syndrome has been reported.

Acute myeloblastic leukemia (AML) is a group of malignant bone marrow neoplasms of myeloid

precursors of white blood cells. Acute myelomonocytic leukemia (AML-M4) is a common type of pediatric AML. However, the condition is rare and represents approximately 3% of all leukemias during childhood and has an incidence of 1.1 – 1.7 per million per year. The symptoms may be aspecific: asthenia, pallor, fever, dizziness and respiratory symptoms. More specific symptoms are bruises and/or (excessive) bleeding, coagulation disorders (DIC), neurological disorders and gingival hyperplasia. Diagnostic methods include blood analysis, bone marrow aspirate for cytochemical, immunological and cytogeneticalanalysis, and cerebrospinal fluid (CSF) investigations. A characteristic chromosomal abnormalityobserved in AML-M4 is inv(16). Treatment includes intensive multidrug chemotherapy and in selected cases allogeneic bone marrow transplantation. Nevertheless, outcome of AML remains poor with an

overall survival of 35-60%. Children with AML-M4 carrying the inv(16) abnormality have a better prognosis (61% 5-year overall survival). New therapeutics are required to increase the probability of cure in this serious disorder.

Myelodysplastic–myeloproliferative diseases are a category of hematological malignancies disorders created by the World Health Organization which have characteristics of both myelodysplastic and myeloproliferative conditions.

When a hematological malignancy is characterised by normal differentiation of cells of myeloid cell line, it is referred to as myeloproliferative. On the other hand, when there is abnormal differentiation of cells of myeloid cell line, it is referred to as myelodysplastic.

Refractory cytopenia of childhood (RCC) is a subgroup of myelodysplastic syndrome (MDS), having been added to the World Health Organization classification in 2008. Before then, RCC cases were classified as childhood aplastic anemia. RCC is the most common form of MDS in children and adolescents, accounting for approximately half of all MDS cases.

Refractory anemia with excess of blasts (RAEB) is a type of myelodysplastic syndrome with a marrow blast percentage of 5% to 19%.

In MeSH, "Smoldering leukemia" is classified under RAEB.

The bone marrow of patients with RCC contains islands of erythroid precursors and spare granulocytes. In some scenarios, multiple bone marrow biopsy examinations may be recommended before a diagnosis can be established.

Bone marrow biopsy shows abnormal megakaryocytes, macrocytic erythropoiesis, and defects in neutrophil production and fibrosis of the marrow (myelofibrosis).

Clinically patients present with reduction in the count of all blood cells (pancytopenia), a very few blasts in the peripheral blood and no or little spleen enlargement (splenomegaly).

Cells are usually CD34 positive.