Page 373 - Textbook of Pathology, 6th Edition

reciprocal translocation between chromosomes 9 and 22, 357
 TABLE 14.4: WHO Classification of Myeloid Neoplasms.
forming Philadelphia chromosome. The t(9;22) involves
I. MYELOPROLIFERATIVE DISEASES fusion of BCR (breakpoint cluster region) gene on
1. Chronic myeloid leukaemia (CML), {Ph chromosome t(9;22) chromosome 22q11 with ABL (named after Abelson murine
(q34;11), BCR/ABL-positive}
2. Chronic neutrophilic leukaemia leukaemia virus) gene located on chromosome 9q34. The
3. Chronic eosinophilic leukaemia/ hypereosinophilic syndrome fusion product so formed is termed “Ph chromosome t(9;22)
4. Chronic idiopathic myelofibrosis (q34;11), BCR/ABL” which should be positive for making
5. Polycythaemia vera (PV) the diagnosis of CML. This identification may be done by
6. Essential thrombocythaemia (ET) microsatellite PCR or by FISH. The underlying patho-
7. Chronic myeloproliferative disease, unclassifiable physiologic mechanism of human CML is based on the
II. MYELODYSPLASTIC/MYELOPROLIFERATIVE DISEASES observation that BCR/ABL fusion product proteins are
1. Chronic myelomonocytic leukaemia (CMML) capable of transforming haematopoietic progenitor cells in
III. MYELODYSPLASTIC SYNDROME (MDS) vitro and form malignant clone. BCR/ABL fusion product
1. Refractory anaemia (RA) brings about following functional changes:
2. Refractory anaemia with ring sideroblasts (RARS) i) ABL protein is activated to function as a tyrosine kinase
3. Refractory cytopenia with multilineage dysplasia (RCMD) enzyme that in turn activates other kinases which inhibits
4. RCMD with ringed sideroblasts (RCMD-RS) apoptosis. CHAPTER 14
5. Refractory anaemia with excess blasts (RAEB-1) ii) Ability of ABL to act as DNA-binding protein is altered.
6. RAEB-2 iii) Binding of ABL to actin microfilaments of the cytoskeleton
7. Myelodysplastic syndrome unclassified (MDS-U) is increased.
8. MDS with isolated del 5q
Exact mechanism of progression of CML to the blastic
IV. ACUTE MYELOID LEUKAEMIA (AML) phase is unclear but following mechanisms may be involved:
1. AML with recurrent cytogenetic abnormalities i) Structural alterations in tumour suppressor p53 gene.
i) AML with t(8;21)(q22;q22) ii) Structural alterations in tumour suppressor Rb gene.
ii) AML with abnormal bone marrow eosinophils {inv(16)
(p13q22)} iii) Alterations in RAS oncogene.
iii) Acute promyelocytic leukaemia {t(15;17)(q22;q12)} iv) Alterations in MYC oncogene.
iv) AML with 11q23 abnormalities (MLL) v) Release of cytokine IL-1β.
2. AML with multilineage dysplasia vi) Functional inactivation of tumour suppressor protein,
i) With prior MDS phosphatase A2.
ii) Without prior MDS
3. AML and MDS, therapy-related Clinical Features
i) Alkylating agent-related Chronic myeloid (myelogenous, granulocytic) leukaemia
ii) Topoisomerase type II inhibitor-related
iii) Other types comprises about 20% of all leukaemias and its peak incidence
4. AML, not otherwise categorised is seen in 3rd and 4th decades of life. A distinctive variant of Disorders of Leucocytes and Lymphoreticular Tissues
i) AML, minimally differentiated CML seen in children is called juvenile CML. Both sexes are
ii) AML without maturation affected equally. The onset of CML is generally insidious.
iii) AML with maturation Some of the common presenting manifestations are as under:
iv) Acute myelomonocytic leukaemia (AMML) 1. Features of anaemia such as weakness, pallor, dyspnoea
v) Acute monoblastic and monocytic leukaemia and tachycardia.
vi) Acute erythroid leukaemia 2. Symptoms due to hypermetabolism such as weight loss,
vii) Acute megakaryocytic leukaemia
viii) Acute basophilic leukaemia lassitude, anorexia, night sweats.
ix) Acute panmyelosis with myelofibrosis 3. Splenomegaly is almost always present and is frequently
x) Myeloid sarcoma massive. In some patients, it may be associated with acute
pain due to splenic infarction.
V. ACUTE BIPHENOTYPIC LEUKAEMIA
4. Bleeding tendencies such as easy bruising, epistaxis,
menorrhagia and haematomas may occur.
The WHO classification of myeloproliferative disorders 5. Less common features include gout, visual disturbance,
includes 7 types as shown in Table 14.4. Classic and common neurologic manifestations and priapism.
examples are chronic myeloid leukaemia (CML), 6. Juvenile CML is more often associated with lymph node
polycythaemia vera (PV), and essential thrombocytosis (ET), enlargement than splenomegaly. Other features are frequent
each one representing corresponding excess of granulocytes, infections, haemorrhagic manifestations and facial rash.
red blood cells, and platelets, respectively. The group as a
whole has slow and insidious onset of clinical features and Laboratory Findings
indolent clinical behaviour.
The diagnosis of CML is generally possible on blood
picture alone. However, bone marrow, cytochemical stains
CHRONIC MYELOID LEUKAEMIA (CML)
and other investigations are of help.
Definition and Pathophysiology I. BLOOD PICTURE. The typical blood picture in a case
By WHO definition, CML is established by identification of of CML at the time of presentation shows the following
the clone of haematopoietic stem cell that possesses the features (Fig. 14.13):