TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13.
Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies.
Two known genes map within the critically deleted region of 12p: TEL, the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27.
Among these genetic variations, Philadelphia-negative gain-of-function mutation in the janus kinase 2 (JAK2) protein leads to overexpression of the genes involved in cell growth and proliferation, and has been linked to development of hematological malignancies, specifically, myeloproliferative neoplasms (MPNs; essential thrombocythemia [ET], polycythemia vera [PV], and primary myelofibrosis).
CALR mRNA quantification using real-time polymerase chain reaction revealed it to be significantly higher in AML compared with other hematologic malignancies (P < 0.0001).
There have been a number of studies on the incidence of P-GP expression in tumor cells or tissues, where detectable level of P-GP has been found in all types of hematological malignancies.
The standardization of methods for P-gp, permitting large multicentric studies, and the results of randomized studies with modifier agents will help us know if mdr1 gene overexpression is of clinical importance in hematologic malignancies.
Chemoresistance in some hematologic malignancies has been associated with overexpression of P-glycoprotein, which is encoded by the MDR1 gene (also known as PGY1).
The data demonstrate that overexpression of MDR1 and MRP genes in hematological malignancies elevates in patients after chemotherapy and correlates with poor clinic prognosis and more frequent recurrences of the malignancies.
The assay established will enable the quantification of MDR1 gene expression in blood samples from patients with leukemic hematologic malignancies and will be applicable to clinical laboratories as a routine test.
Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies.
Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.