Myelodysplastic and Myeloproliferative Neoplasms
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Direct answer
Myelodysplastic syndromes are clonal stem cell diseases of ineffective haematopoiesis — cytopenias with dysplastic morphology but blasts below 20 per cent — that may progress to acute myeloid leukaemia, while myeloproliferative neoplasms are clonal overproductions: polycythaemia vera with JAK2 mutation and a raised haematocrit, essential thrombocythaemia with platelets above 450 thousand per microlitre, primary myelofibrosis with a dry tap and teardrop cells, and chronic myeloid leukaemia defined by the Philadelphia chromosome and its BCR-ABL1 fusion. Blast percentage separates MDS from acute leukaemia at 20 per cent, and mutation testing has become the fastest way to sort the myeloproliferative group.
What you must remember
- MDS morphology: macrocytic anaemia refractory to therapy, hypogranular and pseudo-Pelger-Huet (bilobed) neutrophils, ring sideroblasts on iron stain, and micromegakaryocytes — these four findings on a marrow read-out are the diagnosis.
- MDS risk stratification: blasts decide — excess blasts type 1 is 5–9 per cent and type 2 is 10–19 per cent with the highest progression risk; 20 per cent or more blasts is acute myeloid leukaemia.
- The 5q minus syndrome: isolated del(5q) — macrocytic anaemia, hypolobated megakaryocytes, better prognosis, and a striking response to lenalidomide; a favourite single-gene answer.
- Polycythaemia vera: JAK2 V617F in about 95 per cent; haemoglobin above 16.5 grams per decilitre in men and 16.0 in women, erythropoietin characteristically low, aquagenic pruritus, splenomegaly, thrombosis including Budd-Chiari syndrome in young women; phlebotomy plus low-dose aspirin.
- Essential thrombocythaemia: platelets over 450 thousand per microlitre with JAK2, CALR or MPL mutations; bleeding and thrombosis both, and CALR-mutated younger patients run a more benign course.
- Primary myelofibrosis: dry tap on aspiration, teardrop red cells, leucoerythroblastic film, massive splenomegaly from extramedullary haematopoiesis; mutation pattern the same trio.
- Chronic myeloid leukaemia: t(9;22) Philadelphia chromosome producing BCR-ABL1 p210; basophilia in the blood; chronic phase progressing through accelerated phase to blast crisis; tyrosine kinase inhibitors transformed its prognosis.
- Natural histories converge: polycythaemia vera and essential thrombocythaemia may burn out into secondary myelofibrosis, and any of them may transform to acute leukaemia.
Two patients, one laboratory
Walk two referrals through the same haematology laboratory. The first is a 71-year-old with fatigue and a mean corpuscular volume of 104 femtolitres; B12 and folate are normal, and the reticulocyte count is inappropriately low. Ineffective erythropoiesis is the concept: the marrow is hypercellular yet the blood is empty because clones die in situ. The aspirate shows dysplastic megakaryocytes and, on Perls stain, ring sideroblasts — nucleated red cells with iron-loaded mitochondria ringing the nucleus; molecular testing for SF3B1 supports the low-blast, relatively favourable category. His management is supportive — transfusions, with hypomethylating agents if blasts climb, and transplantation reserved for the fit few.
The second is a 56-year-old fisherman with a ruddy complexion, headaches after hot baths (aquagenic pruritus) and a haemoglobin of 19 grams per decilitre. The reasoning fork is polycythaemia vera versus secondary polycythaemia, and one hormone resolves it: erythropoietin is low in vera (the clone does not obey it) and high with hypoxia, smoking, erythropoietin-secreting tumours or exogenous use. JAK2 V617F confirms vera; treatment is phlebotomy to a target haematocrit below 45 per cent, low-dose aspirin, and cytoreduction with hydroxycarbamide for those already thrombosed. Both patients are then followed for the same convergent end points — spent-phase fibrosis or blast transformation — because the myeloproliferative and myelodysplastic worlds meet at the acute leukaemia boundary.
Where students slip
Macrocytysis is reflexively called B12 deficiency and the patient is sent home with vitamins; a refractory macrocytic anaemia with normal B12 and a low reticulocyte count deserves a marrow, and the pseudo-Pelger-Huet neutrophil on the film is the silent clue students photograph but do not recognise. In the polycythaemias, the erythropoietin level is the forgotten discriminator. And in chronic myeloid leukaemia, candidates quote the Philadelphia chromosome but not the basophilia or the fact that blast crisis may be myeloid or lymphoid — the latter treated with regimens borrowed from acute lymphoblastic leukaemia.
Frequently asked questions
What blast percentage separates MDS from acute myeloid leukaemia?
Twenty per cent — myelodysplastic syndromes sit below it, classified by degree of dysplasia and blast excess; 20 per cent or more defines acute leukaemia.
Which mutation defines polycythaemia vera and which finding confirms it?
JAK2 V617F in about 95 per cent, with a low serum erythropoietin distinguishing it from secondary polycythaemia.
What characterises the 5q minus syndrome?
Isolated deletion of 5q — macrocytic anaemia, hypolobated megakaryocytes, relatively good prognosis and response to lenalidomide.
Which myeloproliferative neoplasm produces a dry tap with teardrop cells?
Primary myelofibrosis — fibrotic marrow, extramedullary haematopoiesis in the spleen, and a leucoerythroblastic blood picture.
What is the genetic lesion of chronic myeloid leukaemia?
The t(9;22) Philadelphia chromosome creating the BCR-ABL1 fusion tyrosine kinase, targeted by imatinib and later-generation inhibitors.
Why does essential thrombocythaemia cause bleeding as well as thrombosis?
The massively expanded, often dysfunctional platelet population consumes von Willebrand factor and forms aggregates; high counts paradoxically impair primary haemostasis.