Hematology

Microcytic Anaemia A problem in haemoglobin results in the improper folding in RBC leading to a reduced cell mass. – Due to the structure of haemoglobin, it is caused by deficits in haem group or Hb chains themselves.   Iron Deficiency Anaemia (IDA) This is a microcytic anaemia which occurs due to decreased levels of iron, most common worldwide.   Causes: – Blood loss –> GI bleeding or menstruation (seen in 14% of women) – Poor diet –> seen in babies or children – Malabsorption –> coeliac disease, due to inflammation of the small bowel   Symptoms: – General signs

Normocytic Anaemia This refers to anaemia with normal-sized RBCs (MCV = 80-100). It is mainly due to 2 types of disease: – Increased peripheral destruction –> haemolytic anaemias – Underproduction by the bone marrow –> aplastic anaemia, chronic kidney disease – To distinguish between peripheral destruction and underproduction by the bone marrow, you look at the reticulocyte count  Reticulocyte Count   Intravascular Haemolysis These conditions involve destruction of RBCs within blood vessels and lead to following signs: – Haemoglobinaemia –> raised free plasma Hb in serum – Haemoglobinuria –> this causes tea-coloured urine – Decreased Plasma haptoglobin –> This mops

Myeloproliferative Disorders This is a neoproliferation of mature cells of the myeloid lineage – it is a disease of late adulthood – Cells of all myeloid lineages are increased but the disease is classified based on main cell type produced. – They are associated with mutations in JAK2 kinase – Main complications are risk of ­ ↑ uric acid (gout) due to high cell turnover, bone marrow fibrosis and progression to an acute leukaemia.    Polycythaemia Vera (RBC) This is a proliferation of RBCs, which are unusual as they do not require erythropoietin to survive – Almost all of these

Plasma Cell Disorders Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia

Lymphomas This is a neoplastic proliferation of lymphocytes which accumulate in lymph nodes or tissue forming a mass – They are divided into Hodgkin’s lymphoma (characterized by Reed-Sternberg Cells) and Non-Hodgkin’s   Hodgkin Lymphoma (HL) This is a malignant proliferation of Reed-Sternberg (RS) cells. These are large B cells with prominent nucleoli in their multilobed nuclei (owl eyed nuclei) – The RS cells are CD15 and CD30, and secrete cytokines giving B cell symptoms – They attract inflammatory cells which make up the tumour bulk – It usually occurs in a bimodal distribution – seen in 20s and in 60-70-year-old

Acute Leukaemia This is the neoplastic proliferation of (WBC precursors “blasts”), defined as >20% blasts in bone marrow – Increased blasts disrupt normal hematopoiesis, resulting in a quick-onset presentation with anaemia (fatigue), thrombocytopenia (bleeding) and neutropenia (infection).   Acute Lymphoblastic Leukaemia (ALL) This is a neoplastic proliferation of immature lymphoblasts in the bone marrow, which leads to bone marrow failure and tissue infiltration. It is the most common malignancy of childhood (rarer in adults) – The cancer cells have a marker, which is the enzyme TdT and are divided into B or T cell lymphoblasts – B cell lymphoblasts display

Platelet Disorders These can arise due to decreased bone marrow production, excess destruction or poor functioning – These abnormalities are divided into quantitative (low platelet count due to bad supply or removal) and qualitative disorders (where there is a problem with the structure or function of the platelet) – Clinical features usually involve mucosal and skin bleeding. – Skin bleeding –> leads to petechiae + Purpura (3mm) + Easy bruising. – Mucosal bleeding –> leads to epistaxis (most common symptom) + GI bleeding + hematuria Qualitative Platelet Disorders   Immune Thrombocytopenic Purpura (ITP) This is an autoimmune production of antibodies

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Anaemia: Overview Anaemia is defined as a low haemoglobin (Hb) concentration, which can be either due to a reduced RBC mass or increased plasma volume (e.g. in pregnancy) – It is <135g/L for men and <115g/L for women – Subdivided by the mean corpuscular volume (MCV) into microcytic (MCV<80um3), normocytic (80-100) and macrocytic (MCV > 100).   Symptoms: – Weakness, fatigue and dyspnea – Pale conjunctiva and skin – Headaches + light headedness – Angina –> especially if there is pre-existing coronary artery disease (+ aortic flow murmur) – Can be signs of a hyperdynamic circulation due to compensation (tachycardia,

Plasma Cell Disorders Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia

This is a group of rare disease causes by various errors of porphyrin biosynthesis, genetic or acquired. – Porphyrin is made in a series of enzyme reactions. – Depending on the faulty part, there is accumulation of either porphyrinogens (unstable precursors of porphyrins) or initial reactants like d-aminovulinic acid. – The initial reactants are neurotoxic, whilst porphyrins induce photosensitivity + free radical formation.   Acute intermittent porphyria This is an autosomal dominant condition due to a defect in porphobilinogen deaminase, which is much more common in females – The results in the toxic accumulation of d-aminolaevulinic acid and porphobilinogen –

Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   – If not

Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia –> increase bone

This is a neoproliferation of mature cells of the myeloid lineage – it is a disease of late adulthood – Cells of all myeloid lineages are increased but the disease is classified based on main cell type produced. – They are associated with mutations in JAK2 kinase – Main complications are risk of ­ ↑ uric acid (gout) due to high cell turnover, bone marrow fibrosis and progression to an acute leukaemia.    Polycythaemia Vera (RBC) This is a proliferation of RBCs, which are unusual as they do not require erythropoietin to survive – Almost all of these patients have

Lymphomas This is a neoplastic proliferation of lymphocytes which accumulate in lymph nodes or tissue forming a mass – They are divided into Hodgkin’s lymphoma (characterized by Reed-Sternberg Cells) and Non-Hodgkin’s   Hodgkin Lymphoma (HL) This is a malignant proliferation of Reed-Sternberg (RS) cells. These are large B cells with prominent nucleoli in their multilobed nuclei (owl eyed nuclei) – The RS cells are CD15 and CD30, and secrete cytokines giving B cell symptoms – They attract inflammatory cells which make up the tumour bulk – It usually occurs in a bimodal distribution – seen in 20s and in 60-70-year-old

Leukaemias This is a neoplastic proliferation of WBC cell types which do not form a mass, divided into acute and chronic: Leukhaemias will usually be diagnosed in the follow pathway: – FBC –> shows raised WBC count – Blood smear –> shows presence of tumour cells in the blood – Bone marrow biopsy with immunophenotyping is diagnostic –> shows >20% blasts with cell markers – CT staging scan allows for staging and to look for organ involvement NICE Referral Guidelines   Acute Leukaemia This is the neoplastic proliferation of (WBC precursors “blasts”), defined as >20% blasts in bone marrow –

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Platelet Disorders These can arise due to decreased bone marrow production, excess destruction or poor functioning – These abnormalities are divided into quantitative (low platelet count due to bad supply or removal) and qualitative disorders (where there is a problem with the structure or function of the platelet) – Clinical features usually involve mucosal and skin bleeding. – Skin bleeding –> leads to petechiae + Purpura (3mm) + Easy bruising. – Mucosal bleeding –> leads to epistaxis (most common symptom) + GI bleeding + hematuria Qualitative Platelet Disorders   Immune Thrombocytopenic Purpura (ITP) This is an autoimmune production of antibodies

Normocytic Anaemia This refers to anaemia with normal-sized RBCs (MCV = 80-100). It is mainly due to 2 types of disease: – Increased peripheral destruction –> haemolytic anaemias – Underproduction by the bone marrow –> aplastic anaemia, chronic kidney disease – To distinguish between peripheral destruction and underproduction by the bone marrow, you look at the reticulocyte count  Reticulocyte Count   Intravascular Haemolysis These conditions involve destruction of RBCs within blood vessels and lead to following signs: – Haemoglobinaemia –> raised free plasma Hb in serum – Haemoglobinuria –> this causes tea-coloured urine – Decreased Plasma haptoglobin –> This mops

Haematology Principles Blood cells are made from heamatopoietic stem cells in bone marrow which differentiate into either: – Common myeloid progenitors – Lymphoid progenitors, which give rise to lymphocytes.   One of the most important types of cells is the red blood cell. – Formed from an erythroid progenitor called reticulocyte. – Its role is to carry oxygen to tissues around the body In order to make red blood cells, you have to make the cellular precursors and haemoglobin:   Cellular precursors: To make reticulocytes, folic acid is needed for thymidine synthesis to make DNA – This needs Vitamin B12,

Introduction Sickle cell disease refers to a group of conditions that are characterised by inheritance of sickle haemoglobin. Sickle cell disease (SCD) is one of the most common inherited disorders. It is caused by inheritance of an abnormal beta globin gene, which leads to sickle haemoglobin. It is classified as one of the haemoglobinopathies. Haemoglobinopathies Haemoglobinopathies refer to a group of genetic diseases that affect the structure of haemoglobin. They can be broadly divided into two types: Haemoglobin variants: mutant forms of haemoglobin that affect its structure. Sickle cell disease is the most recognised. Thalassaemia: reduced or absent globin chain production due

Introduction Polycythaemia vera (PV) is a myeloproliferative disorder caused by the clonal proliferation of hematopoietic progenitor cells. PV is characterised by an elevation in the red cell mass, typically manifesting as a raised haemoglobin or haematocrit on a full blood count (FBC). It is often accompanied by elevated platelets and/or neutrophils. Around 98% of cases are linked to an acquired mutation of Janus Kinase 2 (JAK2), a tyrosine kinase important in cell signaling pathways. It may be diagnosed incidentally or symptomatically with features like headache, visual disturbance and pruritis or with thrombotic/haemorrhagic complications. Treatment involves reducing the red cell mass, either

Overview Non-Hodgkin lymphomas are the sixth most common type of cancer in the UK. Lymphoma is a haematological malignancy arising from lymphoid tissue. They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma: Hodgkin lymphoma (HL): Characterised by the presence of Hodgkin/Reed-Sternberg cells (large, multinucleated cells). Further categorised as classical Hodgkin’s lymphoma (nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted) and nodular lymphocyte-predominant Hodgkin’s lymphoma. Non-Hodgkin lymphoma (NHL): Reed-Sternberg cells are not seen in NHL. There are more than 60 subtypes and they can be B-cell or NK/T-cell in origin. B-cell lymphomas are more common accounting for around 80%, though there is significant geographic variation. NHLs

Overview Multiple myeloma refers to a malignant disorder of plasma cells (mature B lymphocytes). Multiple myeloma (MM) is the second most common haematological malignancy. It is characterised by excess secretion of a monoclonal antibody. We term it a monoclonal antibody, because it is derived from a single clone of plasma cells that have undergone abnormal proliferation. MM accounts for 60-70 cases per 1,000,000 people each year, although the overall prevalence of the condition is increasing due to the improved survival with newer treatments. Unfortunately, it still accounts for 2% of cancer-related deaths and it is associated with a number of severe complications

Overview Microcytic anaemia describes the presence of a reduced haemoglobin concentration and a reduction in the mean corpuscular volume (MCV). Normal RBC haemoglobin (Hb) concentration for males is approximately 130-175 g/L and for females 120-155 g/L. Hb concentration below these levels is considered to be anaemic. The MCV describes the mean volume of erythrocytes and is measured in femtolitres (fL). The standard range for erythrocytes is 82-99 fL. Levels < 82 fL are considered microcytic. There are numerous causes of a microcytic anaemia: Iron-deficiency anaemia (IDA) Anaemia of chronic disease Thalassaemias (e.g. alpha / beta) Iron-deficiency anaemia IDA is the most common cause of anaemia worldwide. Epidemiology IDA

Overview Macrocytic anaemia describes the presence of a reduced haemoglobin concentration and an increase in the mean corpuscular volume (MCV). Normal RBC haemoglobin concentration for males is approximately 130-175 g/L and for females approximately 120-155 g/L. A haemoglobin (Hb) concentration below this levels is considered to be anaemic. The MCV describes the mean volume of erythrocytes and is measured in femtolitres (fL). The standard range for erythrocytes is 82-99 fL. Levels > 99 fL are considered macrocytic. There are numerous causes of a macrocytic anaemia. These can be divided into the megaloblastic (which include B12 and folate deficiency) and non-megaloblastic anaemias (which include a

Overview Hodgkin lymphomas are characterised by the presence of Hodgkin/Reed-Sternberg cells. Lymphoma is a haematological malignancy arising from lymphoid tissue. They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma: Hodgkin lymphoma (HL): Characterised by the presence of Hodgkin/Reed-Sternberg cells. Further categorised as classical Hodgkin’s lymphoma (nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted) and nodular lymphocyte-predominant Hodgkin’s lymphoma. Non-Hodgkin lymphoma (NHL): Reed-Sternberg cells are not seen in NHL. There are more than 60 subtypes and they can be B-cell or NK/T-cell in origin. B-cell lymphomas are more common accounting for around 80%, though there is significant geographic variation. NHLs are more common than Hodgkin lymphoma,

Overview Haematopoiesis describes the process by which the cellular components of the blood are formed. In adults, the predominant site of haematopoiesis is the bone marrow. Here we find the multipotent hematopoietic stem cells (HSCs). The HSCs are able to differentiate into both myeloid or lymphoid cell lines. Furthermore, the ability to self-renew facilitates continued production of blood cells. Haematopoiesis is essential to the continued production of all blood cell lineages. Three major cell types exist; red blood cells (erythrocytes), white blood cells (leucocytes) and platelets (thrombocytes). ​ Leucocytes are further divided into a number of specialised cell types, including monocytes,

Overview Glucose-6-phosphate dehydrogenase deficiency is an X-linked inherited disorder that predisposes to haemolytic anaemia. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the inherited haemolytic anaemias. It is an X-linked inherited disorder due to a genetic variant (i.e. mutation) in the gene that encodes the protein G6PD located on the long arm of the X chromosome. G6PD is needed for the formation of nicotinamide adenine dinucleotide phosphate (NADPH) that is used to maintain stores of glutathione in red blood cells that has a crucial role in preventing oxidative damage. The condition is usually asymptomatic but characterised by episodes of anaemia due to haemolysis

Overview Deep vein thrombosis is a common condition due to partial or total occlusion of a deep vein. Venous thromboembolism Venous thromboembolism (VTE) is a term that encompasses two conditions: Pulmonary embolism (PE): acute/chronic occlusion of pulmonary arteries. Clot breaks off and travels to the lungs (emboli). Deep vein thrombosis (DVT): acute/chronic occlusion of deep vein(s). Commonly affects the lower limbs through the formation of a clot forms (thrombus). VTE is commonly asymptomatic, but 1-2 per 1000 people every year have symptomatic VTE. DVT accounts for two thirds of these cases and is commonly seen with PE. It is estimated that 80% of cases

Introduction Chronic myeloid leukaemia (CML) is a clonal myeloproliferative neoplasm characterised by abnormal clonal expansion of cells of the myeloid lineage. Leukaemia Leukaemia refers to a group of malignancies that arise in the bone marrow. They are relatively rare but together are the 12th most common cancer in the UK, responsible for around 4,700 deaths a year. There are four main types: Acute myeloid leukaemia (AML) Acute lymphoblastic leukaemia (ALL) Chronic myeloid leukaemia (CML) Chronic lymphocytic leukaemia (CLL) Presentation, prognosis and management all depend on the type and subtype of leukaemia. Chronic myeloid leukaemia The condition is characterised genetically by the Philadelphia (Ph) chromosome, an abnormal

Overview Chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia in adults in Western countries. Leukaemia Leukaemia refers to a group of malignancies that arise in the bone marrow. They are relatively rare but together are the 12th most common cancer in the UK, responsible for around 4,700 deaths a year. There are four main types: Acute myeloid leukaemia (AML) Acute lymphoblastic leukaemia (ALL) Chronic myeloid leukaemia (CML) Chronic lymphocytic leukaemia (CLL) Presentation, prognosis and management all depend on the type and subtype of leukaemia. Chronic lymphocytic leukaemia CLL is considered a lymphoproliferate disorder of B lymphocytes, which results from an abnormal clonal expansion

Overview Thalassaemia refers to a group of disorders characterised by reduced or absent globin chain production. Thalassaemia is one of the haemoglobinopathies, which refers to a group of autosomal recessive inherited disorders that affect the globin chains that form the protein component of haemoglobin. Haemoglobinopathies Haemglobinopathies can be broadly divided into two types: Haemoglobin variants: mutant forms of haemoglobin that affect the structure. Sickle cell disease is most well recognised. Thalassaemia: reduced or absent globin chain production due to underlying mutations. Thalassaemia Thalassaemia can be further divided depending on the type of globin chain affected: Alpha thalassaemia: reduced or absent production of

Definition The World Health Organisation (WHO) defines anaemia by the following haemoglobin (Hb) concentrations: Males < 130 g/L (130-175 g/L) Females < 120 g/L (120-155 g/L)* * In pregnancy, a Hb < 110 g/L is diagnostic. Strictly speaking, anaemia is defined as a reduction in circulating red blood cell mass. However, in clinical practice, anaemia is defined by more measurable variables such as: Red blood cell (RBC) count Haemoglobin (Hb) concentration Haematocrit Hb concentration is commonly used in the assessment of anaemia.​ It is important to understand that anaemia is a manifestation of an underlying problem, not a diagnosis in itself. Its recognition warrants

Overview Thalassaemia refers to a group of disorders characterised by reduced or absent globin chain production. Thalassaemia is one of the haemoglobinopathies, which refers to a group of autosomal recessive inherited disorders that affect the globin chains that form the protein component of haemoglobin. Haemoglobinopathies Haemglobinopathies can be broadly divided into two types: Haemoglobin variants: mutant forms of haemoglobin that affect the structure. Sickle cell disease is most well recognised. Thalassaemia: reduced or absent globin chain production due to underlying mutations. Thalassaemia Thalassaemia can be further divided depending on the type of globin chain affected: Alpha thalassaemia: reduced or absent production of

Introduction Acute myeloid leukaemia occurs due to the malignant transformation and proliferation of myeloid progenitor cells. Leukaemia Leukaemia refers to a group of malignancies that arise in the bone marrow. They are relatively rare but together are the 12th most common cancer in the UK, responsible for around 4,700 deaths a year. There are four main types: Acute myeloid leukaemia (AML) Acute lymphoblastic leukaemia (ALL) Chronic myeloid leukaemia (CML) Chronic lymphocytic leukaemia (CLL) Presentation, prognosis and management all depend on the type and subtype of leukaemia. Acute myeloid leukaemia In AML proliferation of abnormal myeloid progenitor cells is seen. It refers to a heterogeneous group

Introduction Acute lymphoblastic leukaemia is the most common malignancy of childhood. Leukaemia Leukaemia refers to a group of malignancies that arise in the bone marrow. They are relatively rare but together are the 12th most common cancer in the UK, responsible for around 9,900 cases and 4,700 deaths a year. There are four main types: Acute myeloid leukaemia (AML) Acute lymphoblastic leukaemia (ALL) Chronic myeloid leukaemia (CML) Chronic lymphocytic leukaemia (CLL) Presentation, prognosis and management all depend on the type and subtype of leukaemia. Acute lymphoblastic leukaemia ALL arises from a clone of lymphoid progenitor cells that undergo malignant transformation. Most are B-cell in origin