Promyelocytic leukemia (PL) is a hematopoietic malignancy and more specifically a type of acute myelogenous leukemia (AML), which is characterized by the increased levels of promyelocytes. Promyelocytes are partly differentiated granulocytes, which develop from a myeloblast into the final, completely differentiated myelocyte.
Patients who are affected by promyelocytic leukemia exhibit decreased numbers of all three types of blood cells: erythrocytes, leukocytes and platelets. Therefore, patients affected by the condition are expected to present with fatigue and pallor caused by anemia, frequent infections and fever due to the leukocytopenia and hematuria or a general hemorrhagic tendency due to the low platelet count.
Thrombocytopenia is a potentially fatal complication, as it can follow disseminated intravascular coagulation (DIC) and threaten the life of the patient, leading to a mortality rate of up to 20% of sudden deaths . The pathophysiologic process that induced DIC in patients with promyelocytic leukemia is not fully clarified yet; it is believed, however, that an augmented rate of multifactorial fibrinolytic activity is responsible for the phenomenon .
The central nervous system can also be affected by promyelocytic leukemia, but this is more commonly observed during a relapse rather than at the time of the initial episode  .
The first step towards a successful diagnosis involves laboratory blood testing. Patients with promyelocytic leukemia exhibit low counts of all lines of blood cells. The pancytopenia also causes abnormal results in other tests, such as a prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), high levels of fibrin D-dimer and hypofibrinogenemia.
Another test that is essential for the characterization of a condition as PL is a bone marrow biopsy. The aspirate tests positive to Sudan black and myeloperoxidase. The bone marrow itself can be either hypogranular or hypergranular, with the latter amounting to approximately 75% of the cases . Histologically, promyelocytes are irregular, with azurophilic granulation. The Auer rods are the most typical histologic finding and constitute structures shaped like needles, which are found in the cytoplasm of the promyelocytes.
The hypergranular PL type, which is the most common disease type diagnosed, exhibits increased auto-fluorescence blasts during an immunophenotyping study. Genetic evaluation is also mandatory in order for a decisive diagnosis to be established: fluorescence in situ hybridization (FISH) and standard cytogenetic techniques are amongst the methods that are able to detect the translocation or the fused RARA-PML gene . The polymerase chain reaction by reverse transcriptase (RT-PCR) is a popular method as well.
Promyelocytic leukemia treatment is based on a protocol which calls for an initial induction therapy, followed by consolidation therapy and then maintenance therapy. A specific treatment scheme has been established for relapses of the disease as well. The induction therapy includes the administration of all-trans retinoic acid (ATRA), chemotherapy which contains anthracycline and possibly arsenic trioxide (ATO).
Consolidation therapy also consists of ATO and ATRA, so that the potential risk of relapse can be calculated. Patients who display relapses are either treated with ATO or with a stem cell transplantation; both autologous and allogeneic stem cell transplantation can be performed with none having a therapeutic advantage over the other .
PL is a hematopoietic malignancy accompanied by a poor prognosis in patients that have been newly diagnosed. The actual mortality rate and general prognosis vary considerably, depending on the type of proteins expressed by the cells; it has been observed that CD56+, CD3+ and CD2+ immunophenotypes constitute poor prognostic factors. Such patients are faced with a higher mortality and a greater risk of relapses    .
Almost every single occurrence of promyelocytic leukemia is a result of a genetic mutation, that leads to the fusion of two distinct genes: the PML gene (promyelocytic leukemia gene) with the RARA gene, which stands for retinoic acid receptor alpha gene . Both genes are involved in the hematopoietic procedure under normal circumstances; the PML protein, encoded for by the PML gene, functions as a tumor suppressor and partakes in the regulation of apoptosis, whereas RARA regulates the function of retinoic acid (RA), which, in turn, influences the differentiation process of promyelocytes into neutrophils. The specific mutation that leads to these two genes being conjoined is the t(15;17)(q22;q21) translocation, but various other translocations may lead to the same leukocytic phenotype, although they are very rarely observed.
In a considerable number of cases, promyelocytic leukemia is accompanied by other congenital defects, with trisomy 8 being the most commonly diagnosed one. A minority of PL cases may be induced by prior chemotherapy or radiotherapy.
Promyelocytic leukemia is a condition primarily diagnosed in adults between the ages of 20 to 60 years old; it evinces no sex predilection . Radiation therapy or chemotherapy can occasionally lead to PL. It has been calculated that out of all cases of acute myeloid leukemia, approximately 15% of the cases fall into the sub-group of promyelocytic leukemia, amongst the target group of adult people; in some regions, the percentage may be even higher, such as in Brazil (28%), Mexico (20%) and other locations      .
Promyelocytic leukemia is a malignancy caused by a genetic mutation. In the greatest majority of the cases, this mutation encompasses a translocation between the PML and RARA genes and is described as t(15;17)(q22;q21). The mutation occurs following conception, and therefore cannot be inherited.
The PML gene, or promyelocytic gene, is located on chromosome 15. Its function has not been thoroughly investigated but it is believed to play a significant role in the process of cellular death and in tumor suppression. On the other hand, the RARA gene, located on chromosome 17, functions based on the concentrations of retinoic acid: in its presence, RARA is activated and mediates the differentiation of promyelocytes. If retinoic acid is unavailable, the nuclear corepressor factor attaches itself onto the gene and transcription is hindered.
The translocation that occurs between the two aforementioned genes gives rise to a new, abnormal PML-RARA protein that leads to the need for higher concentrations of retinoic acid, in order for the gene to be activated.
In a minority of PL cases, the translocation does not involve the PML gene, but the translocation occurs between RARA and other genes, such as PZLF, nucleophosmin, STAT5b, NuMa, ORF2BP2 . The type of genes involved in the mutation that leads to PL is indeed significant because it alters the therapeutic interventions that will prove effective against the disease . Additional genetic abnormalities that may accompany PL are not believed to contribute to the prognosis either positively or negatively.
There are no established guidelines concerning the prevention of promyelocytic leukemia, due to the fact that its causes remain undefined. However, the avoidance of various risk factors that have been linked to the condition is advised, such as ionizing radiation, smoking, benzene, obesity and electromagnetic fields.
Promyelocytic leukemia (PL) is a hematopoietic malignancy, caused by a genetic mutation in the myeloid cells. It constitutes 5 to 10% of adult leukemias and is frequently a type of cancer with a rapid progression . The mutation involves a translocation that leads to the fusion of two genes, mostly the retinoic acid receptor alpha gene (RARA) and promyelocytic leukemia gene (PML). Both genes partake in the hematopoietic process and regulate various functions such as apoptosis, differentiation and tumor suppression.
Promyelocytic leukemia primarily affects the adult population and is diagnosed in the ages of 20 to 60 years old. It is a rather uncommon type of malignancy, which has been calculated to affect approximately 1 out of 1,000,000 individuals in the European region.
Due to the fact that the condition leads to pancytopenia, the symptoms are caused due to the inadequacy of all three lines of cells. Fatigue, weakness, pallor, weight loss, dyspnea, and fever are the initial, nonspecific symptoms that patients usually present with. A hemorrhaging tendency is also noticed with its main manifestations being hematuria, epistaxis and bleeding gums.
Diagnosis is achieved via laboratory blood testing which reveals pancytopenia, in combination with a bone marrow biopsy that is expected to yield results including a hyper- or hypogranular bone marrow with increased numbers of promyelocytes. Genetic confirmation is also required and can be achieved through various techniques.
Treatment includes the administration of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy or ATRA and arsenic trioxide. Consolidation therapy is also employed, as a means of eliminating the residual malignant cells. As a last resort, after a drug-refractory relapse, autologous or allogeneic stem cell transplantation can be opted for, although this is rarely required.
Promyelocytic leukemia (PL) is a type of cancer that affects the bone marrow, and, subsequently, the blood. It can occur at any age, but adults between the ages of 20 and 60 are most commonly affected by it.
The bone marrow is a vital organ, that is responsible for the production and maturation of all of the cellular components of the blood: red blood cells, white blood cells and platelets. In cases of PL, the white blood cells do not develop properly and experience a very early arrest in their maturation process. As a result, they are released into the circulation at an earlier developmental stage and are too immature to fight infections and diseases. Moreover, these immature cells, called lymphoblasts, progressively replace the material that the bone marrow is made of and lead to a decreased production of red blood cells and platelets as well.
Patients with PL present with a variety of symptoms. Decreased concentrations of red blood cells lead to anemia, fatigue and weakness; fewer platelets imply a tendency towards hemorrhaging and the presence of immature white blood cells leads to the inability of the organism to protect itself against infections.
Promyelocytic leukemia is diagnosed with a complete blood count and a bone marrow biopsy. Radiologic evaluation is necessary to find out whether the malignant cells have infiltrated the brain or spinal cord. The condition is treated with chemotherapy.