HAEMATO-ONCOGENETICS

The BCR/ABL gene is also found in about 5% of paediatric and 25% of adult patients with acute lymphocytic leukaemia (ALL), where the presence of this gene has important prognostic significance. It also occurs in a small proportion (about 2%) of patients with acute myeloid leukaemia (AML). The BCR/ABL fusion gene is a product of the so-called Philadelphia chromosome (Ph), which arises by reciprocal translocation of the long arms of chromosomes 9 and 22 - t(9;22)(q34;q11) and is one of the most common cytogenetic aberrations in haematological malignancies.

Gene, specification: BCR/ABL fusion gene

Type of material to be examined: blood

Indicating specialists: clinical haematology

In a large proportion of patients, the cause is a mutation in the JAK2gene, which encodes an enzyme essential for signal transduction in hematopoietic cells. Mutation p.V617F of the JAK2 gene leads to disruption of autoinhibitory activity and activation of the JAK2 enzyme, resulting in uncontrolled proliferation and survival of hematopoietic cells. This mutation occurs in 65-97% of patients with polycythaemia vera, 30-57% of patients with essential thrombocythemia and 35-95% of patients with chronic idiopathic myelofibrosis. This mutation has also been found in 20% of Ph-negative atypical CML, more than 10% of CMML patients, 15% of patients with megakaryocytic AML (AML M7), and 20% of patients with juvenile myelomonocytic leukaemia.

Gene, specification: JAK2 gene (p.V617F)

Type of material to be examined: blood

Indicating specialists: clinical haematology

In the case of qualitative detection of the p.V617F mutation of the JAK2 gene, this test also allows quantitative evaluation of this mutation. The qPCR method is used to determine the percentage of the mutation in the analysed blood sample

Gene, specification: JAK2 gene (p.V617F)

Type of material to be examined: blood

Indicating specialists: clinical haematology

Detection of a mutation in the JAK2 gene allows confirmation of this diagnosis.

Gene, specification: JAK2 gene, exon 12

Type of material to be examined: blood

Indicating specialists: clinical haematology

In addition to the JAK2 gene, another common cause of the disease is the MPL gene mutation, which occurs in about 5-10% of patients with essential thrombocythemia. MPL is a proto-oncogene found on chromosome 1p34 and encodes a thrombopoietin receptor that is important for the regulation of cell proliferation. Somatic mutations in exon 10 of the MPL gene (mainly W515L, W515K) affect activation of the JAK/STAT signalling pathway (Janus Kinase/Signal Transducers and Activators of Transcription). 

Gene, specification: MPL gene, p.W515L, p.W515K 

Type of material to be examined: blood

Indicating specialists: clinical haematology 

In addition to the JAK2 gene, another common cause of the disease is a mutation in the CALR gene, which occurs in about 25% of patients with essential thrombocythemia. It is also found in 8% of patients with myelodysplasia and in 60-80% of JAK2-negative and MPL-negative patients with primary myelofibrosis. The CALR gene encodes calreticulin, an endocellular enzyme localized in the endoplasmic reticulum, where it binds pathological proteins and prevents their transfer to the Golgi apparatus. All mutations of the CALR gene described so far are insertions and deletions in exon 9, which subsequently cause the formation of a protein with pathological function.

Gene, specification: CALR gene, exon 9

Type of material to be examined: blood

Indicating specialists: clinical haematology

Based on the presence of the Ph chromosome (BCR/ABL fusion gene), MPNs are divided into Ph-positive, which corresponds to chronic myeloid leukemia (CML), and Ph-negative MPNs, which include polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and others.

The common feature of these diseases is the overproduction of one or more hematopoietic cell lines with the finding of hypercellular bone marrow and the washout of mature and fully functional blood elements into the peripheral blood. Advanced stages of each type of MPN may progress to acute leukaemia or myelofibrosis. In patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), the V617F somatic mutation of the JAK2 gene is most frequently detected (in 50-60%), and in another 5-10% mutations of the MPL and CALR genes are detected. According to the latest findings, somatic mutations of other genes ASXL1, CUX1, DNMT3A, EZH2, IDH1, IDH2, KIT, RUNX1, SF3B1, SH2B3, SRSF2, TET2, TP53, U2AF1

Gene, specification: ASXL1, CALR, CUX1, DNMT3A, EZH2, IDH1, IDH2, JAK2, KIT, MPL, RUNX1, SF3B1, SH2B3, SRSF2, TET2, TP53, U2AF1

Type of material to be examined: blood

Indicating specialities: clinical haematology

Delivery time: 15 working days

CLL occurs approximately twice as often in men as in women. The prognosis of a CLL patient can be determined, for example, by the presence or absence of somatic hypermutations of the immunoglobulin variable region heavy chain genes (IGVH). Somatic hypermutations of the IGVH gene represent a physiological process by which antibody diversity normally increases. Patients with the mutated IGVH gene have a significantly better prognosis than patients with the non-mutated gene.

Gene, specification: IGVH gene

Type of material to be examined: blood

Indicating specialists: clinical haematology

Tumour suppressor p53 is a key regulator of cell cycle and apoptosis. The presence of aberrations in the TP53 gene leads to a more aggressive disease course and resistance to therapy in B-CLL patients. In most cases, the TP53 gene is inactivated by a deletion of one allele and a mutation of the other, but there are also single deletions or mutations without damage to the second allele. The difference in prognosis between patients carrying inactivation of both alleles and those with damage to one allele is not yet clear.

Gene, specification: TP53 gene

Type of material to be examined: blood

Indicating specialists: clinical haematology

These genetic changes occur in more than 80% of CLL patients and are used as prognostic markers. Deletion of 13q14 (DLEU1) is one of the most common abnormalities in CLL patients and has a relatively good prognosis. Trisomy of chromosome 12 has a moderate prognosis. The most serious genetic changes include deletion of 11q22 (ATM) and deletion of 17p13 (TP53), which are among the aberrations with unfavourable prognostic value. Accurate characterization of molecular and cytogenetic abnormalities is crucial to better stratify at-risk chronic lymphocytic leukaemia patient groups in order for them to benefit from new therapeutic approaches.

Gene, specification: DLEU1, LAMP1, ATM, TP53 gene + centromere of chromosome 12

Type of material to be examined: blood

Indicating specialists: clinical haematology