What is an Acute Promyelocytic Leukemia?

March 07 23:47 2019 Print This Article

It is defined as a disorder in which there is a cancer of the blood and bone marrow. It is known as the APL. There is a AML with variants and different sub types such as M3. In this there is a accumulation of the immature granulocytes which are known as the pro myelocytes. In this there is a chromosomal trans location which involves the retinoic acid receptor alpha gene and is a unique form in its response to the all trans retinoic acid therapy. It was first characterized in the year 1957. For 20 years it was fatal that is from 1950 to 1970. There was no effective treatment and no one knew how the cancer was formed.

What is the diagnosis of Acute promyelocytic leukemia?

This disorder can be differentiated from the other disorders by the morphological examination of the bone marrow aspirate and biopsy. A definite diagnosis requires he testing of the PML fusion gene. It can be done by the help of polymerase chain reaction which is referred as a PCR. There is a fluorescent in situ hybridization which is referred as a FISH. One can also perform the conventional cyto genetics of the peripheral blood or a bone marrow. It involves the trans location of the long arm chromosomes of 15 and 17. RAR is the member of nuclear family and its ligand a retinoic acid is a form of vitamin A and it acts as a regulator of the transcription of DNA at multiple sites. The monitoring for relapse using PCR test for PML transcript allows early re treatment of the disorder which is quite successful.

What is the pathology of Acute promyelocytic leukemia?

This disorder is characterized by a translocation of the chromosome which involves the gene on the chromosome 17 by a retinoic acid receptor alpha gene. In most of the cases of APL the retinoic acid receptor alpha present on chromosome 17 is involved and plays a role in the reciprocal translocation. It occurs with the pro myelocytic leukemic gene present on the chromosome 15. The translocation is denoted as the subtype t. A RAR receptor depends on the retinoic acid for regulation of transcription.

In the APL fusing there were 4 another genes which were involved and were linked to the pro myelocytic leukemia gene known as the PLZF and nucleo phosmin which is known as the NPM and nuclear matrix associated known as NUMA or single transducer and activator of transcription 5b which is referred as a STAT 5B. All of these arrangements are ATRA sensitive and are resistant to ATRA excluding PLZF. The fusion of PML and RAR forms a hybrid protein which is used to alter functions.

This proteins bind with the increased affinity for the sites present on the DNA cell which block the transcription and the differentiation of granulocytes. It acts by increasing the interaction of nuclear co repressors molecule and histone de acetylase which are referred as a NOCR and HDACL. The chromosomal translocation which involves the RAR is an initiating event and requires additional mutations for the development of leukemia. The APL has a hyper granular form which is used to feature faggot cells and is applied to the blast cells due to the presence of multiple auer rods in the cytoplasm. It gives the appearance of a bundle of sticks from which the cells got their name.

What is the epidemiology of Acute promyelocytic leukemia?

It represents around 6 percent cases of AML in adults. The median age is 40 years which is comparatively in the younger age group as compared to the other type of AMLs. In this the age group is 70 years. If there is no proper medicine and treatment it can lead to death of the patient. This disorder has high rate of relapse with normal chemotherapy. The incidence is increased in the patients who have origin from Latin America.

What are the signs and symptoms of Acute promyelocytic leukemia?

It includes the normal differentiation of white blood cells in the marrow. It starts with the multi potent hematopoietic stem cells which are known as the HSC. The regulation of the gene can occur by the inhibitory and inductive mechanism. There are many transcription factors like PU 1 and C/ EB protein alpha which can be identified and play an important role in the differentiation of white blood cells. The hematopoietic stem cells give rise to lymphoid cells which are B as well as T cells. They also include the myeloid cell line. It haves granules in their cytoplasm and are known as the granulocytes which play an important role in the fighting of infections.

The aggregation of the pro myelocytes plays an important role in the bone marrow with the reduction in the production of normal red blood cells and platelets. It causes anemia and thrombocytopenia. The bone marrow cannot produce a healthy red blood cells and one can observe the leucopenia and leucocytosis in the peripheral blood.

The symptoms include the fatigue, weakness, shortness of breath due to anemia with a decrease in the normal red blood cell production. There is an easy bruising and bleeding which may lead to the blood clotting and occur from the thrombo cytopenia and coagulopathy. There is a fever and infection which occur due to the absence of normal white blood cells. There is an enlargement of the spleen which may lead to the discomfort in abdomen.

Acute pro myelocytic leukemia is associated with the bleeding which is caused by the disseminated intra vascular coagulation which refers to DIC. In this disorder there is a increase in the immature white blood cells which results in the progression of malignant cells and goes inside the bone marrow. It results in low red blood cells lead to the anemia and the low platelet count may lead to serious bleeding.

What is the treatment of Acute promyelocytic leukemia?

It is a unique leukemia due to its sensitivity to the all Trans retinoic acid referred as a ATRA. It is a derivative of vitamin A. The treatment with the ATRA dislocates the NOCR HDACL complex from RAR and helps in the transcription of DNA and in the differentiation of immature leukemic cells into their mature forms by targeting the oncogenic transcription factor and its abbberant action. It reprogram’s the immature leukemic cells to a normal functioning cells. It does not kill as the conventional chemotherapy does and ATRA is combined with the anthra cycline based chemotherapy which results in the clinical remission of 90 percent of the cases.

ATAR alone is capable of inducing remission by the absence of anthracycline but it is short lived. Currently, arsenic tri oxide has been recommended for the treatment of relapsed or refractory disease. The ATRA therapy is associated with the side effects of retinoic acid syndrome. It is associated with the dyspnea, fever and gain in weight. One can also observe the peripheral edema and is treated with the help of dexa methasone.

The etiology of this syndrome is due to the capillary leak syndrome from the cytokine release from the differentiating pro myelocytes. In the case of relapsed or refractory diseases one can go for the allogenic bone marrow or stem cell transplantation. One also observes remission with the use of arsenic tri oxide. The most common element is arsenic which has been used in the Chinese medicines for last 2000 years.

There are few studies which have shown that the arsenic re organized the nuclear bodies and degrades the mutant PML RAR fusion protein. It also increases the caspase activity which induces apoptosis. It decreases the relapse rate for high risk patients.

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