Chronic Myeloproliferative Neoplasms is a group of clonal disorders of the hematopoietic stem cells that lead to an effective proliferation of one or more hematopoietic component in the bone marrow, and in many cases, in the liver and spleen leading to elevated blood levels of one or more myeloid cell lineages (i.e., erythrocytosis, leukocytosis, and thrombocytosis). 

1. Chronic myeloid leukemia (CML - Ph+ve) 

2. Polycythemia vera (PV) 

3. Essential thrombocythemia (ET) 

4. Primary myelofibrosis (PMF) 

These diseases are closely related to each other, and the transition form and evolution from one entity to another occurs during the course of the disease. 

- The vast majority of CML show the Philadelphia chromosome, in (90-95%) and M-BCR-ABL p210 in (99% of patients). Ph chromosome is the tiny chromosome 22 from which the long arm is deleted (22q-). 

It is part of a reciprocal translocation between chromosomes 9 & 22 t (9; 22) in which part of 22 is clearly located on 9 but the part of 9 on 22 is very small to be distinguished cytogenetically. 

This translocation is discovered by PCR or FISH techniques. 

- Almost all PV patients, and about 55% of ET and MF cases show a single acquired mutation of cytoplasmic Janus-Associated Kinase 2 (JAK2) that occurs in the BM 

and in the peripheral blood granulocytes. 

JAK2 plays a great role in normal myeloid development. 

CML is characterized by the proliferation of a population of differentiated cells that leads to a greatly expanded total myeloid mass. 

CML represents about 15 % of leukemias. 

A. Chronic Phase (CP), B. Accelerated Phase (AP), C. Blastic Phase (BP). 

The Chronic phase (CP) usually lasts 2-7 years and in 50% of cases, it is transformed into BP directly. 

In up to 50% of cases, the diagnosis is made incidentally from a routine blood count (asymptomatic). 

May have features of anemia (paleness, difficulty breathing, and Tachycardia) and abnormal platelet function (bruising, epistaxis, and menorrhagia). 

Splenomegaly is almost always present, and it is often enlarged. 

- Anemia; usually normochromic normocytic. 

- Leukocytosis: usually in the range of 20-200 ×109/L. 

- Blood film shows a full spectrum of granulocytic cells, ranging from blasts (usually 2-10%) to mature neutrophils, with intermediate myelocytes and neutrophils predominating. 

- Eosinophils and basophils are usually increased 

- Platelet count is usually increased. 

BM Aspirate: 

- Markedly hypercellular marrow 

- Blast cells < 10% of all nucleated cells (ANC).

 

- increased megakaryocytes which are small and hypolobed. 

 

BM biopsy showed that the fat space was completely lost due to dense hypercellularity. 

 

In advanced diseases (AP and BP), the clinical characteristics are very different: 

- Asymptomatic; the diagnosis is depending completely on blood and marrow findings.

- Patients may have a fever, excessive sweating, anorexia, weight loss, or bone pain. 

- Occasionally, patients present with generalized lymphadenopathy; where LN biopsy shows nodal infiltration with blast cells that may be myeloid or lymphoid. 

- Localized skin infiltrates may be seen. 

Discrete masses of blast cells may develop at almost any site; these are sometimes referred to as "Myeloid Sarcomas". 

In AP: Blasts range (10-19%) in peripheral blood and/or BM, basophils ≥20%. Platelet count is < 100 × 109/L or persistently >1000 × 109/L, increasing spleen size and WBCs unresponsive to therapy. 

There may be a megakaryocytic proliferation in sizable sheets and clusters, associated with marked fibrosis. 

In BP: Blasts >20% in peripheral blood and/or BM, or extramedullary blast proliferation (LN, skin, elsewhere), or detection of large foci or clusters of blasts in BM biopsy. 

- CML patients in the chronic phase usually show an excellent response with the use of imatinib, the 5-year survival is around 90%. 

- The 5-year survival after SCT is approximately 50-70%, providing that SCT is done within the first year following diagnosis. 

- The average survival time of AP patients is 1-2 years. 

- Transformed into acute leukemia and eventually died within 2-6 months. 

- Death occurs from terminal blastic transformation or intercurrent hemorrhage or infection.