Sadaf Shahab

Prognostic Involvement of Nucleophosmin Mutations in Acute Myeloid Leaukemia

Nucleophosmin (NPM1) is a protein of highly conserved nature which works as a molecular chaperone and is mostly found in nucleoli. NPM also involved in the maturation of preribosomes and duplication of centrosomes. Furthermore, it is also active in control and regulation of the ARF-p53 tumor suppressor pathway. A high rate of incidence and prognostic involvement is reported by various authors in AML patients. In AML it behaves as a favorable prognostic marker. NPM mutations are more frequently associated with normal-karyotype AML and are usually absent in patients having abnormal or poor cytogenetic. NPM mutations are not frequent in other hematopoietic tumors .Two main types of mutations have been described to date. Both of these cause abnormal cytoplasmic localization of NPM1. Their high incidence rate in normal karyoptype and their favorable nature make those mutations hot spot or front face mutations which should be checked before treatment starts.

Molecular Involvement and Prognostic Importance of Fms-like Tyrosine Kinase 3 in Acute Myeloid Leukemia

AML (Acute myeloid leukemia) is a form of blood cancer where growth of myeloid cells occurs in the bone marrow. The prognosis is poor in general for many reasons. One is the presence of leukaemia-specific recognition markers such as FLT3 (fms-like tyrosine kinase 3). Another name of FLT3 is stem cell tyrosine kinase-1 (STK1), which is known to take part in proliferation, differentiation and apoptosis of hematopoietic cells, usually being present on haemopoietic progenitor cells in the bone marrow. FLT3 act as an independent prognostic factor for AML. Although a vast literature is available about the association of FLT3 with AML there still is a need of a brief up to date overview which draw a clear picture about this association and their effect on overall survival.

Outcome of Inversion 16 in TKD Positive and Negative Acute Myeloid Leukemia Patients.

abstract.

Chronic Myeloid Leukemia - Prognostic Value of Mutations

Chronic myeloid leukemia (CML) is a stem cell disorder characterized by unrestricted proliferation of the myeloid series that occurs due to the BCR-ABL fusion oncogene as a result of reciprocal translocation t(9;22) (q34;q11). This discovery has made this particular domain a target for future efforts to cure CML. Imatinib revolutionized the treatment options for CML and gave encouraging results both in case of safety as well as tolerability profile as compared to agents such as hydroxyurea or busulfan given before Imatinib. However, about 2-4% of patients show resistance and mutations have been found to be one of the reasons for its development. European Leukemianet gives recommendations for BCR-ABL mutational analysis along with other tyrosine kinase inhibitors (TKIs) that should be administered according to the mutations harbored in a patient. The following overview gives recommendations for monitoring patients on the basis of their mutational status.

Survival Outcome of AML Patients with and without TKD Mutations

Acute myeloid leukaemia (AML) is a disease of heterogenic nature (Su et al., 2013; Ahmad et al., 2014). “Almost one third of AML patients have normal karyotype and fall in a standard risk group” (Kotaridis et al., 2001; Karabacak et al 2010). Significant proportion of AML cases have normal karyotype and characterized by the presence of prognostic markers such as FLT3ITD,(internal tandem duplication) and TKD (point mutation), NPM1 and CEBPA (Ishfaq et al., 20012; Renneville et al., 2014). Tyrosine kinase mutations induce “constitutive tyrosine phosphorylation, enhance cell proliferation and development of hematologic malignancies” (Liang et al., 2003). The clinical and prognostic relevance of the TKD mutations is less clear (Liang et al., 2003) and are more dependent on other mutations as reported by various authors (Thieda et al., 2002). More generally FLT3-TKD mutations is less frequent (7%) than internal tandem duplications (20-25%) (Weisberg et al, 2010). Although, there is “considerable heterogeneity” amongst subtypes. The frequency of FLT3-TKD mutations is not equal in all AML subtypes. The association of FLT3-TKD mutations with outcome is controversial and more difficult to study because of low number of cases (Mead et al, 2008). In order to investigate the role of TKD mutation in TKD positive and TKD negative patient and their effect on overall survival we have examined small cohort of 31 patients. We performed Polymerase chain reaction and gell electrophorhesis (Thiede et al., 2003). The data was analysed with SPSS version20. We have not compared any other haematological parameters, regarding this study, except the overall survival in AML patients on the basis of presence and absence of FLT3-TKD mutation. Independent samples t-test was performed at 0.05 significance level. In statistical test, p-value (0.492>0.05) resulted in insignificant difference between the overall survival of AML patients with and without TKD mutation. Although TKD mutations have controversial outcome generally but there was no significant difference found in overall survival of TKD positive and TKD negative patients in this study.