Although not yet formally incorporated in the generally accepted classification systems, molecular profiling of myelodysplastic syndrome genomes has increased the understanding of prognostic molecular factors for this disease. For example, in low-risk MDS, "IDH1" and "IDH2" mutations are associated with significantly worsened survival.

The Düsseldorf score stratifies cases using four categories, giving one point for each; bone marrow blasts ≥5%, LDH >200U/L, haemoglobin ≤9g/dL and a platelet count ≤100,000/uL. A score of 0 indicates a low risk group' 1-2 indicates an intermediate risk group and 3-4 indicates a high risk group. The cumulative 2 year survival of scores 0, 1-2 and 3-4 is 91%, 52% and 9%; and risk of AML transformation is 0%, 19% and 54% respectively.

The outlook in MDS is variable, with about 30% of patients progressing to refractory AML. The median survival rate varies from years to months, depending on type. Stem-cell transplantation offers possible cure, with survival rates of 50% at 3 years, although older patients do poorly.

Indicators of a good prognosis:

Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow (< 20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal or mixed karyotypes without complex chromosome abnormalities; and "in vitro" marrow culture with a nonleukemic growth pattern

Indicators of a poor prognosis:

Advanced age; severe neutropenia or thrombocytopenia; high blast count in the bone marrow (20-29%) or blasts in the blood;

Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section;

completely or mostly abnormal karyotypes, or complex marrow chromosome abnormalities and "in vitro" bone marrow culture with a leukemic growth pattern

Karyotype prognostic factors:

- Good: normal, -Y, del(5q), del(20q)

- Intermediate or variable: +8, other single or double anomalies

- Poor: complex (>3 chromosomal aberrations); chromosome 7 anomalies

The IPSS is the most commonly used tool in MDS to predict long-term outcome.

Cytogenetic abnormalities can be detected by conventional cytogenetics, a FISH panel for MDS, or virtual karyotype.

The International Prognostic Scoring System (IPSS) was developed in the mid-1990s to assess the prognosis of MDS patients. This system stratifies cases into 2 groups; a lower-risk group (sub divided into low and intermediate-1) and a higher risk (subdivided into intermediate-2 and high). It uses the blast percentage, number of cytopaenias and bone marrow cytogenetics data to place cases of CMML into these groups. Due to the scoring system being developed for MDS, the more myeloproliferative cases of CMML (WBC >13x10) are excluded from the scoring system. Although the IPSS scoring system is used clinically, there is a high variability in each group. For this reason, new modalities for assessing prognosis in MDS (and CMML) are being developed.

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.

Regular full blood counts are required on a regular basis to determine whether the patient is still in a state of remission.

Many patients with aplastic anemia also have clones of cells characteristic of the rare disease paroxysmal nocturnal hemoglobinuria (PNH, anemia with thrombopenia and/or thrombosis), sometimes referred to as AA/PNH. Occasionally PNH dominates over time, with the major manifestation intravascular hemolysis. The overlap of AA and PNH has been speculated to be an escape mechanism by the bone marrow against destruction by the immune system. Flow cytometry testing is performed regularly in people with previous aplastic anemia to monitor for the development of PNH.

The condition needs to be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., leukopenia and thrombocytopenia) resulting in decrease of all formed elements. In contrast, pure red cell aplasia is characterized by reduction in red cells only. The diagnosis can only be confirmed on bone marrow examination. Before this procedure is undertaken, a patient will generally have had other blood tests to find diagnostic clues, including a complete blood count, renal function and electrolytes, liver enzymes, thyroid function tests, vitamin B and folic acid levels.

The following tests aid in determining differential diagnosis for aplastic anemia:

1. Bone marrow aspirate and biospy: to rule out other causes of pancytopenia (i.e. neoplastic infiltration or significant myelofibrosis).

2. History of iatrogenic exposure to cytotoxic chemotherapy: can cause transient bone marrow suppression

3. X-rays, computed tomography (CT) scans, or ultrasound imaging tests: enlarged lymph nodes (sign of lymphoma), kidneys and bones in arms and hands (abnormal in Fanconi anemia)

4. Chest X-ray: infections

5. Liver tests: liver diseases

6. Viral studies: viral infections

7. Vitamin B and folate levels: vitamin deficiency

8. Blood tests for paroxysmal nocturnal hemoglobinuria

9. Test for antibodies: immune competency

The first clue to a diagnosis of AML is typically an abnormal result on a complete blood count. While an excess of abnormal white blood cells (leukocytosis) is a common finding with the leukemia, and leukemic blasts are sometimes seen, AML can also present with isolated decreases in platelets, red blood cells, or even with a low white blood cell count (leukopenia). While a presumptive diagnosis of AML can be made by examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy as well as ruling out pernicious anemia (Vitamin B12 deficiency), folic acid deficiency and copper deficiency.

Marrow or blood is examined under light microscopy, as well as flow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia - ALL), and to classify the subtype of disease. A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent "in situ" hybridization. Genetic studies may also be performed to look for specific mutations in genes such as "FLT3", nucleophosmin, and "KIT", which may influence the outcome of the disease.

Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.

The diagnosis and classification of AML can be challenging, and should be performed by a qualified hematopathologist or hematologist. In straightforward cases, the presence of certain morphologic features (such as Auer rods) or specific flow cytometry results can distinguish AML from other leukemias; however, in the absence of such features, diagnosis may be more difficult.

The two most commonly used classification schemata for AML are the older French-American-British (FAB) system and the newer World Health Organization (WHO) system. According to the widely used WHO criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts, except in the three best prognosis forms of acute myeloid leukemia with recurrent genetic abnormalities (t(8;21), inv(16), and t(15;17)) in which the presence of the genetic abnormality is diagnostic irrespective of blast percent. The French–American–British (FAB) classification is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow (BM) or peripheral blood (PB) for the diagnosis of AML. AML must be carefully differentiated from "preleukemic" conditions such as myelodysplastic or myeloproliferative syndromes, which are treated differently.

Because acute promyelocytic leukemia (APL) has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent "in situ" hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence of PML/RARA fusion protein, which is an oncogenic product of that translocation.

Evidence is conflicting on the prognostic significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival; however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance.

Cure rates in clinical trials have ranged from 20–45%; although clinical trials often include only younger people and those able to tolerate aggressive therapies. The overall cure rate for all people with AML (including the elderly and those unable to tolerate aggressive therapy) is likely lower. Cure rates for promyelocytic leukemia can be as high as 98%.

Definitive diagnosis of a chloroma usually requires a biopsy of the lesion in question. Historically, even with a tissue biopsy, pathologic misdiagnosis was an important problem, particularly in patients without a clear pre-existing diagnosis of acute myeloid leukemia to guide the pathologist. In one published series on chloroma, the authors stated that 47% of the patients were initially misdiagnosed, most often as having a malignant lymphoma.

However, with advances in diagnostic techniques, the diagnosis of chloromas can be made more reliable. Traweek et al. described the use of a commercially available panel of monoclonal antibodies, against myeloperoxidase, CD68, CD43, and CD20, to accurately diagnose chloroma via immunohistochemistry and differentiate it from lymphoma. Nowadays, immunohistochemical staining using monoclonal antibodies against CD33 and CD117 would be the mainstay of diagnosis. The increasingly refined use of flow cytometry has also facilitated more accurate diagnosis of these lesions.

There are two internationally accepted treatment protocols, which are geographically based:

- North America: the Children’s Oncology Group (COG) JMML study

- Europe: the European Working Group for Myelodysplastic Syndromes (EWOG-MDS) JMML study

The following procedures are used in one or both of the current clinical approaches listed above:

Prognosis refers to how well a patient is expected to respond to treatment based on their individual characteristics at time of diagnosis. In JMML, three characteristic areas have been identified as significant in the prognosis of patients:

Without treatment, the survival [5 years?] of children with JMML is approximately 5%. Only Hematopoietic Stem Cell Transplantation (HSCT), commonly referred to as a bone marrow or (umbilical) cord blood transplant, has been shown to be successful in curing a child of JMML. With HSCT, recent research studies have found the survival rate to be approximately 50%. Relapse is a significant risk after HSCT for children with JMML. It is the greatest cause of death in JMML children who have had stem cell transplants. Relapse rate has been recorded as high as 50%. Many children have been brought into remission after a second stem cell transplant.

Symptoms result from underproduction of red blood cells (weakness, pallor, failure to thrive, pica), white blood cells (recurrent or overwhelming infection), and/or platelets (bleeding).

Bone marrow transplant is the only known curative treatment.

Many patients eventually develop acute myelogenous leukemia (AML). Older patients are extremely likely to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers. Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer. Many patients do not reach adulthood.

The overarching medical challenge that Fanconi patients face is a failure of their bone marrow to produce blood cells. In addition, Fanconi patients normally are born with a variety of birth defects. A good number of Fanconi patients have kidney problems, trouble with their eyes, developmental retardation and other serious defects, such as microcephaly (small head).

Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

However, the influential WHO Classification (published in 2001) placed a greater emphasis on cell lineage.

Relative proportions of hematological malignancies in the United States

For the analysis of a suspected "hematological malignancy", a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.

Ringed sideroblasts are seen in the bone marrow.

The anemia is moderate to severe and dimorphic. Microscopic viewing of the red blood cells will reveal marked unequal cell size and abnormal cell shape. Basophilic stippling is marked and target cells are common. Pappenheimer bodies are present in the red blood cells. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but MCV may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.

In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased.

Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B.

1- Congenital: 80% are responsive, though the anemia does not completely resolve.

2- Acquired clonal: 40% are responsive, but the response may be minimal.

3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.

Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.

FA patients are at elevated risk for the development of AML defined as presence of 20% or more of myeloid blasts in the marrow or 5 to 20% myeloid blasts in the blood. All of the subtypes of AML can occur in FA with the exception of promyelocytic. However, myelomonocytic and acute monocytic are the most common subtypes observed. Many MDS patients' diseases evolve into AML if they survive long enough. Furthermore, the risk of developing AML increases with the onset of bone-marrow failure.

Although risk of developing either MDS or AML before the age of 20 is only 27%, this risk increases to 43% by the age of 30 and 52% by the age of 40. Historically, even with a marrow transplant, about a quarter of FA patients diagnosed with MDS/ALS have died from MDS/ALS-related causes within two years, although more recent published evidence suggests that earlier allogeneic hematopoietic progenitor cell transplantation in children with FA is leading to better outcomes over time.

There are several groups where screening for PNH should be undertaken. These include patients with unexplained thrombosis who

are young, have thrombosis in an unusual site (e.g. intra-abdominal veins, cerebral veins, dermal veins), have any evidence of hemolysis (i.e. a raised LDH), or have a low red blood cell, white blood cell, or platelet count. Those who have a diagnosis of aplastic anemia should be screened annually.

PNH is classified by the context under which it is diagnosed:

- "Classic PNH". Evidence of PNH in the absence of another bone marrow disorder.

- "PNH in the setting of another specified bone marrow disorder" such as aplastic anemia and myelodysplastic syndrome (MDS).

- "Subclinical PNH". PNH abnormalities on flow cytometry without signs of hemolysis.

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.

Most affected people have a stable clinical course but are often transfusion dependent.

Lenalidomide has activity in 5q- syndrome and is FDA approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndrome (MDS) associated with chromosome 5q deletion with or without additional cytogenetic abnormalities. There are several possible mechanisms that link the haploinsufficiency molecular lesions with lenalidomide sensitivity.