Leukemia

LEUKEMIA 19

(InstitutionalAffiliation)

is a group of cancer diseases that originates from the bone marrowleading to the formation of large number of white blood cells. Thedeveloped white blood cells are not developed fully and arebiologically referred to as leukemia or blast cells. Major symptomsof leukemia are bruising, bleeding, tiredness, increased risks toinfections and fever. The symptoms arise from lack of effective bloodcells. Diagnosis of leukemia involves bone marrow biopsy and bloodtests.

Theexact cause of leukemia has never been established but is believed tocome from multiple causes. In particular, leukemia is inherited ormay be predisposed by the environment factors. Predisposing factorsinvolves ionizing radiations, smoking, and exposure to some form ofchemicals such as benzene, Down syndrome and prior chemotherapy.Largely, leukemia is genetic and Individuals from families withhistory of leukemia have higher risks (Cancer org. 2014).

exist in four different types Chronic lymphocytic (CLL), acutemyeloid (AML), acute lymphoblastic leukemia (ALL) and Chronic myeloidleukemia (CML). Lymphomas and leukemias fall under the group oftumors that affect human blood, the lymphoid system and the bonemarrow(Egawa, 2004).Treatments of leukemia involve various combinations o f radiation,targeted, chemotherapy, and transplant of bone marrow(Masihi, 2001).In addition, there are supportive care treatments and palliativecare.

Otherless adverse types of leukemia are managed through watchful waitingmethod. Although there are different approaches in treating leukemia,the success of any treatment method depends on the type of leukemiaand the age of the patient (Cancer org. 2014). Treatment of leukemiaare more advanced in developed worlds with an average survival ratesbeen 57% in U.S. Children, under fifteen years of age has a survival rate chance of 60% to 80% based on the type of leukemia suffered.Patients treated from acute leukemia and have over five years ofcancer free are likely to be fully healed (Cancer org. 2014).

Accordingto recent statistics in 2012, increased to 352, 000 leadingto over 265,000 deaths. is identified as the most commontype of cancer among small children with many children suffering fromALL type of leukemia. However, over 90 percent of leukemia cases havebeen diagnosed from adults with most adults suffering from AML andCLL. Further studies indicate that, leukemia occurs mostly indeveloped world (Cancer org. 2014).

TheGenetics of and how it is formed

Thehuman body has 46 Chromosomes in each cell which exist as 23 pairs(U.SNational Library of Medicine. 2014).These chromosomes exist in two copies chromosome 16 is inheritedfrom each parent and form a pair. Chromosomes 16 exists in over 90million DNA representing 3 percent of DNA in human cells (U.SNational Library of Medicine. 2014).Several types of genetic related conditions are attributed to changesin Chromosome 16. These changes involve structural or number ofcopies of chromosomes in the DNA.

Asa result of changes on chromosome 16, genetic problems such as16p11.2 deletion syndrome, alveolar capilar dysplasia and cancerdiseases arises(U.S National Library of Medicine. 2014).The 16p11.2 deletion syndrome arises when one or two copies ofchromosomes are affected 16 in each cell. The effect of thesedeletion leads to missing genes and this in turn results in delayeddevelopment, intellectual disability, development disorders, socialinteraction and communication problems (Autism spectrum disorders)(U.S National Library of Medicine. 2014).In other cases, 16p11.2 deletion syndrome leads to obesity where theaffected individuals have increased risks of seizures. In some cases,16p11.2 duplication arises when an extra copy of 600kb segment ofchromosomes results (Cancer org. 2014).

Changein chromosome 16 structure lead to several types of cancer. Inparticular, this is due to such aspects as translocations andrearrangement of chromosomes. Myelodysplastic syndrome leukemia andchronic myeloid leukemia are associated with these chromosome changes(U.SNational Library of Medicine. 2014).Acute myeloid leukemia is associated with chromosomal rearrangementof chromosome 16. Chromosome 21 is another copy of chromosome that isinherited from each parent and is the smallest (U.SNational Library of Medicine. 2014).

Thecondition of acute myeloid leukemia arises when there is arearrangement of chromosomes 16 (U.SNational Library of Medicine. 2014).In this case, the chromosome breaks into two pieces of DNA. The DNAis reversed and inserted into the chromosome 16. These geneticchanges are attributed to eight percent of AML cancer in adults(Cancerorg. 2014).The genes mutations are acquired during one’s lifetime are presentin all cells (CancerOrg. 2014).The CBFB produces genes that interact with other proteins such asRUNXI to form complex core binding factor (CBF). This complexdevelopment is attached to specific areas of DNA and in theproduction of blood cells (Inaba,Greaves and Mullighan, 2013).This complexity leads to the impairment of CBF the CBF-MYHII blocksCBF DNA interfering with its ability to control gene activity. Tothis end the block in gene activity leads to interference in geneactivity of the blood cells (U.SNational Library of Medicine. 2014).The results are the development of abnormal, immature blood cells.Additional genetic changes lead to myeloid bursts developing intocancerous cells (Seiter,2014).

Inthe case of acute promyelocytic leukemia, the mutation of genes iscaused by two genes chromosomes 15 and chromosome 17 or the RARAgene (Cancerorg. 2014).In this case, a rearrangement of chromosomes 15 and 17 leads to thefusion of PML gene with RARA gene (Inaba,Greaves and Mullighan, 2013).This fusion leads to the production of PML-RARA protein. The proteincontrols the transcription of certain genes that facilitates thematuration of white blood cells. Ideally the PML gene regulates cellsreproductionand the formation of PML-RAR leads to the interference of normal cellreduction (U.SNational Library of Medicine. 2014).As a result, blood cells are stuck at promyelocyte stage leading tothe accumulation of abnormal white blood cells in the bone marrow.The overall result is interference with normal white blood cellproduction. The fusion of PML-RARA leads to 98 percent conditionsleading to acute promyelocytic leukemia (U.SNational Library of Medicine. 2014).As such, acute promyelocytic is not inherited but results fromtranslocation of cells during production (PennMedicine. 2014).

Chromosome21 exists in over 48 million blocks of DNA forming 2 percent of DNAin human cells (U.SNational Library of Medicine. 2014).In the same way, the structure and quantity of chromosome 16 resultsin different genetic problems, changes in chromosome 21 leads tovarious genetic heath problems (Weinblatt,2013).In particular, some type of acute myeloid leukemia is associated withchromosome 21 changes and rearrangement of chromosome 21 leads to 7percent of acute myeloid leukemia (Cancerorg. 2014).The Core binding factor of acute myeloid leukemia (CBF-AML) resultswhen there is translocation of chromosomes 21(U.SNational Library of Medicine. 2014).

Thetranslocation t (8:21) results when part of chromosome 8 fuses withpart of chromosomes 21 (RUNX1T1gene). This fusion produces t (8:21) translocation called theRUNX1-ETO that creates two individual proteins. RUNXI proteinproduces RUNXI gene which is complex gene (core binding factor (CBF)(Cancer org. 2014).The core binding factor inhibits genes involved in blood celldevelopment the RUNX1T1turns off the gene activity (Inaba,Greaves and Mullighan, 2013).Change in gene activity blocks the maturation of blood cells leadingto increased production of abnormal and immature white blood cellsknown as the myeloid blast (Byrd,2014).However, more addition changes to t(8:21) are needed to develop into cancerous cells (Weinblatt,2013).

Otherconditions involve the Down syndrome that is associated withintellectual disability, facial appearance and weak muscles among theinfants. Biologically, Down syndrome results when extra copies ofchromosomes 21 in some body cells (U.SNational Library of Medicine. 2014).Medical studies reveal that having extra copies of chromosome 21leads to disrupting in the normal development of cells leading toincrease health problems (Egawa,2004).Similarly, structural and translocation problems of chromosome 21lead to other several types of cancer such as acute lymphoblasticleukemia that is diagnosed at child hood (U.SNational Library of Medicine. 2014).

Typesof leukemia

Theclassification of leukemia is done based on the degree of acutenessand chronic condition. Acute leukemia is conspicuous for increasednumber of immature blood cells (U.SNational Library of Medicine. 2014).The increased production of immature blood cells leads to crowding inthe bone marrow and hence inhibiting production of healthy bloodcells (Penn Medicine. 2014). Immediate treatment is required foracute case of leukemia to tone down the rapid accumulation andprogression of the malignant cells. When the acute leukemia conditionsets in it spreads to other organs through the blood stream. Acuteleukemia is the most common condition among children(Hutter, 2010).

Chronicleukemia is known for excessive build up of fairly mature butabnormal white blood cells. The chronic condition may take months orseveral years before progressing to other areas. In the case ofchronic leukemia, cells production is at a higher rate than thenormal rate. This results in several abnormal white blood cells.Unlike the acute leukemia that requires immediate treatment, chronicleukemia requires monitoring before treatment is done for optimalefficiency of therapy used (Hutter,2010).Chronic leukemia is found among older people but not limited to age.

  1. Acute lymphoblastic leukemia (ALL)

Acutelymphoblastic leukemia (ALL) is an acute type of cancerous leukemia.The ALL leukemia is conspicuous due to overproduction of cancerousimmature white blood cells referred to as lymphoblast (Seiter,2014).Patients with ALL leukemia develop lymphoblast overproductioncondition in the bone marrow (U.SNational Library of Medicine. 2014).The multiplication of abnormal white blood cells progresses atalarming rate and lead to adverse damage and eventual death of thepatient (Penn Medicine. 2014). In particular, the overproduction ofimmature white blood cells inhibits the production of red bloodcells, white blood cells and the platelets. This conditioninfiltrates to other parts of the body(Inaba,Greaves and Mullighan, 2013).

ALLleukemia is prevalent among young children at age 2-5 years while inother cases it peaks at old age (Hutter,2010).Reliable data indicates that over six thousand cases of ALL arereported in the U.S each year (Seiter,2014).Other unverified data indicate that ALL leukemia is common in U.S,Costa Rica and Italy. Treatment and cure of ALL stands at 80% amongyoung children while 40% among the adults (Inaba,Greaves and Mullighan, 2013).ALL was the first leukemia type to respond positively tochemotherapeutic treatment such as amniptein, methotrexate andantifolates developed in the 40s (U.SNational Library of Medicine. 2014).

Causesand predisposing factors

ALLresults from damaged DNA leading to unregulated production ofimmature white blood cells. ALL leukemia is associated with excessiveexposure to radiation and chemicals presence in animal and humanbodies (Inaba,Greaves and Mullighan, 2013).Excessive radiation exposure is the leading risk factor in ALLleukemia. Progressive studies indicate that prolonged exposure tocertain chemical lead to ALL condition (Penn Medicine. 2014).

Unconfirmedstudies indicate that ALL condition also affects individuals who havebeen treated from other cases of cancer using chemotherapy andradiation (Kimura,Ashihara and Maekawa, 2006).ALL leukemia is diagnosed through bone marrow biopsy, physicalexamination and blood tests. ALL type of leukemia is common in malesthan females. For instance, according to data collected in 2010 U.S,more incidences of ALL were recorded from boys than girls (Seiter,2014).Effective treatment of ALL leukemia depends on the urgency ofdetection. Early detection of ALL leukemia leads to effectivetreatment.

  1. Acute myeloid leukemia (AML)

Acutemyeloid leukemia (AML) is also referred to as acute non-lymphocyticleukemia (ANLL). AML is a type of cancer characterized by rapid andabnormal growth of leucocytes cells (Weinblatt,2013).The abnormal white blood cells overcrowd in the bone marrowinhibiting normal production of blood cells (Cancer org. 2014). AMLis a common leukemia that affects adults and incidences of theconditions increases with age. However, AML leukemia is rare andresults in roughly 1 % deaths reported in U.S (Cancer org. 2014). AMLcondition worsens with age. There are other several subtypes of AMLcondition, prognosis and treatment depending on the subtype (Cancerorg. 2014).

Causesof AML leukemia

Majorcauses of AML leukemia include a number of risk factors such asexposure to hazardous chemicals, radiation ionizers and heredityfactors (Seiter,2014).Preleukemia which is a blood disorder condition may lead to AMLleukemia (Cancer org. 2014). Chemical exposures that increase therisk of AML condition include organic solvents, benzene and othercarcinogenetic substances (Cancer org. 2014). Radiations such asX-rays, nuclear and other radiation rich elements accelerate risks ofAML condition (Colvinand Elfenbein, 2003).Families with a history of AML leukemia lead to several congenitalconditions of AML (Weinblatt,2013).

Diagnosisof AML infection

Completeblood count tests helps in assessing the existence of AML condition.In this case, excess number of white blood cells may infer leukemicblasts (Seiter,2014).Blood tests also may also show decreased red blood cells andplatelets which signify likelihood of AML condition. Other testsinclude bone marrow biopsy tests(Weinblatt, 2013).Acute myeloid leukemia is curable but effective treatment and curefor patients with AML depends on number of factors such as thesubtype of AML(Colvin and Elfenbein, 2003).Epidemiologically, AML is a relatively rare leukemic cancer occurringin 1% of reported cases of blood cancer(Seiter, 2014).

  1. Chronic lymphocytic leukemia (CLL)

Chroniclymphocytic leukemia (CLL) mostly affects the adults (Byrd,2014).The CLL affects the B-cell lymphocytes present in the bone marrowleading to the development of lymph nodes. B cells productionincrease in the bone marrow and blood inhibiting the development andgrowth of healthy blood cells (Janssen,2011).Ideally, chronic lymphocytic leukemia (CLL) occurs as a stage in thedevelopment of small lymphoma (SLL) present in the lymph nodes. CLLis considered adult leukemia affecting individuals at age 50 andmajority of the patients being men (U.SNational Library of Medicine. 2014).In rare cases, the diseases also affect children and teenagers(Byrd, 2014).Research and DNA analysis has led to the identification of two CLLconditions that have different survival rates CLL positive and CLLnegative. The initial method adopted for treating CLL conditiondepends on exact diagnosis and disease progression(Gribben, 2008).In addition, the method used may depend on clinical experience of themedical officer. Several types of agents are used in CLL therapy(Motohashi,2009).

  1. Chronic myeloid leukemia (CML)

Chronicmyeloid leukemia (CML) is also referred to as chronic granulocyticleukemia (CGL)(Provan and Gribben, 2010).CML is white blood cells cancer despicable for high number ofunregulated growth of myeloid cells. In CML leukemia, maturegranulocytes cells overcrowd the bone marrow. CML condition isattributed to chromosomal translocation. Improved research hasenabled the production of targeting drugs that improve survival ratesof CML patients. Patients are able to have quality life using thetargeting drugs (tyrosine kinase inhibitors (TKIs) than traditionalchemotherapy drugs (Besa,Buehler, Markman and Sacher, 2013).

CMLis diagnosed through blood tests to assess the level of granulocytecells. Bone marrow biopsy is also performed. Cytogenetic is anotherdiagnostic method that is used to assess the chromosomal abnormality(U.SNational Library of Medicine. 2014).CML was the first leukemia condition that was found to have stronglinks with genetic factors. CML condition arises from chromosomaltranslocation and is classified into three phases chronic phase,accelerated phase and the blast crisis (Provanand Gribben, 2010).Drug treatment helps to stop the progression if detection is madeearly. The blast crises stage exhibit similar predisposition as acuteleukemia. CML has limited symptoms and most patients realize thecondition during the accelerated and blast crisis. Research indicatesthat over 85% of patients get diagnosis at chronic phase. The chronicphase is asymptomatic but mild symptoms such as fatigue, hip pain andabdominal fullness may be experienced(Provan and Gribben, 2010).

Improvingtreatment methods of

Chemotherapy

Chemotherapyis a cancer treatment method that uses special chemical substancesknown as anti-cancer drugs. These drugs are prescribed for curativeintent, to prolong the patient’s life or to reduce symptoms(palliative chemotherapy). Chemotherapy is one of the majorpharmacotherapy for cancer conditions along with targeted andhormonal therapy (Zhukovand Tjulandin, 2008).Chemotherapy drugs help in killing abnormal cells that is the mainaspect in cancer diseases. One notable aspect of chemotherapy isdecreased production of blood cells (immunosuppressant), loss of hairand inflammation on digestive tract lining (U.SNational Library of Medicine. 2014).

Chemotherapyregimens are used in the treatment acute lymphoblastic leukemia(ALL). This involves a combination of different treatments such asmultiple ant leukemic drugs. Chemotherapy is also effective intreating acute myeloid leukemia (AML). In these treatments,Chemotherapy is done in phases remission induction, intensificationand maintenance therapy. The aim of remission induction is to killrapid cancerous cells from the blood.

Remissioninduction chemotherapy is followed by intensification chemotherapythat involves the use of high doses of intravenous multidrug.Maintenance chemotherapy is done to eliminate any residue cells thatwere not killed in remission as intensification regimens. In allacute case of leukemia, maintenance chemotherapy is effective ininhibiting relapse of cancerous cells.

Treatingacute promyelocytic leukemia (APL)

AcutePromyelocytic leukemia (APL) is a version of acute myelogenousleukemia (AML) where abnormal accumulation of immature white bloodcells is prevalent(Tefferi, 2006).Acute Promyelocytic leukemia (APL) is one of the most treatable formsof leukemia with higher survival rates. Patients experiences anemia,fatigue, weakness, dyspnea, low platelets, bruising and nose bleeding(Bishop, 1997).APL results from chromosomal translocation of chromosome 17 (RARA),APL is distinguishable from other aspects of AML through bone marrowbiopsy examination.

APLtreatment is unique due to its sensitivity to all-trans retinoic acid(ATRA tretinoin). ATRA does not kill malignant cells directly but iseffective with time after administration (Tefferi,2006).In 2013, Arsenic trioxide became the standard remission treatment forAPL in chemotherapy(Lacroix, 2014).Another treatment method for APL is through consolidationchemotherapy. Consolidation chemotherapy is used to prevent relapseand enhance the survival rates of patients (Bishop,1997).

Stemcell transplants

Stemcell transplants refer to the transportation from the bone marrow orperipheral blood cells in the treatment of leukemic cancers(Kane, 2008).In this case, the patient’s immune system is destroyed throughradiation or chemotherapy before cell transportation. Stem celltransplant is a dangerous procedure and only done when the patientlife is threatened. Stem cell transplant is notably used in most typeof leukemia (U.SNational Library of Medicine. 2014).

Stemcell transplant involves the extraction of hematopoietic stem cells(HSC) which may be replaced after the harmful cells have beendestroyed (Gribben,2008).There are two types of stem cells grafts allogenic and autologous.Autologous involves the use of patient’s stored stem cells whileallogeneic may be donated from other people (U.SNational Library of Medicine. 2014).Autologous is mostly preferred for less complications involving theimmune system (Gribben,2008).

Targetedtherapies

Targetedtherapies are a form of chemotherapy for cancer conditions. Targetedtherapies apply the principle of targeted cells to destroy cancerouscells(Zhukov and Tjulandin, 2008).Targeted therapy focuses on reducing the spread of malignant cellsthrough pharmacotherapy. Targeted therapies may combine differenttreatments to kill harmful cells(Lacroix, 2014).There are different forms of targeted therapies such as cytotoxictherapy, biologic therapy and immunotherapy (U.SNational Library of Medicine. 2014).Targeted therapies are effective in breast cancer, prostate cancerand leukemic cancers. The main categories of targeted therapy aremonoclonal antibodies and small molecules. Examples include Tyrosinekinase inhibitors (Zhukovand Tjulandin, 2008).Targeted therapies do not work like the standard chemotherapy but‘targets’ the inner workings if harmful cells.

Immunotherapy

Immunotherapyis a treatment method that involves inducing, suppressing andenhancing immune response (Masihi,2001).Immunotherapy may activate or suppress the immune response systemdepending n the condition and effect intended. In cancer cases,immunotherapy is used to activate the immune system in response toharmful cells. Immunotherapy involves the administration of cytokines(Motohashi, 2009).The cytokines lead to the development of antigens that in turn fightthe cancerous cells(Kimura, Ashihara and Maekawa, 2006).Although immunotherapy is effective, it results in significant sideeffects such as allergies and immune tolerance.

Recentstudies on leukemia

Recentstudies reveal that research on treatment therapies is still oncourse. In a recent study by a Pennsylvanian University oninvestigative therapy made from patients’ own cells, revealed thatover 90% of patient with acute lymphoblastic leukemia (ALL) relapsedand failed to respond to standard therapies. The Pennsylvanian studyis part of the modern immunotherapy methods used to treat acute casesof leukemia where other options have failed (Penn Medicine, 2014).

Arecent study from San Francisco University found that some subtypesof childhood leukemia (ALL) are treatable with new target drugs. Thenew treatment drugs are ibrutiniband idelalisibthat target the B-cells thereby reducing the mutation process. Thesetarget drugs are effective when used in high doses for young childrenduring chemotherapy (Huimin, Christian, Kyle, Zhengshan, Dirk,Thompson, Natalya, Wei-Yi Chen, et al. 2015). In another study,physicians warned against the use of inbrutinib therapy in CLLleukemia because of higher relapse rates (Kami, Amy, Gerard, Nyla,Weiqiang, Lynne, Arletta, Melanie et al, 2015).

Astechnological advancement takes place scientists are making greatprogress in understanding the DNA and leukemia. In particular, recentstudies have focused on chromosomal translocations in order to assesshow the abnormalities could be corrected. Since each case of leukemiais different from the other, recent research is focused onunderstanding the gene behavioral changes as part of study onimproved target therapies. In addition, further studies are conductedon traditional treatment methods as part of improving theireffectiveness when treating leukemia condition (Cancer Org. 2014).For instance, currently researchers are studying new form ofchemotherapy drugs such as Sapacitabine, Laromustine and Tipifarnibfor treating AML leukemia (Cancer org. 2014).

Inanother case, Studies on treatment methods of Acute Promyelocyticleukemia (APL) have found that, a combination of ATRA and arsenictrioxide chemotherapies leads to improved cure. In addition,researchers are still studying the effectiveness of autologous andallogeneic methods of stem transplants. In immunotherapy, morestudies have been focused on the development of new vaccine therapysuch as immune checkpoint inhibitors and other antibodies. These newvaccines would improve the responsiveness of the immune systemagainst various types of leukemia(Jabbour, Cortes, Giles, O`Brien and Kantarjian, 2007).

Conclusion

starts in the human marrow after complexities in the development ofgenes. Complexities in gene development lead to abnormalities inwhite blood cell development. results when there are changesin the gene structure and the translocation of cells in the bonemarrow leads to the development of various kinds of leukemia.However, the exact cause of leukemia is unknown but it is presumed toarise from inherited and environmental factors. Risk factors includeprolonged exposure to ionizing radiations, smoking and somechemicals. The various kinds of leukemia are acute lymphocyticleukemia (ALL), Chronic myeloid leukemia (CML), acute myeloidleukemia (AML) and chronic lymphocytic leukemia (CLL).

is treated through major treatments such as chemotherapy, radiationtherapy, targeted therapy, immunotherapy and bone marrow transplant.In other cases, supportive, palliative and watchful waiting are usedto treat leukemia conditions. The success of leukemia treatmentdepends on the age of the patient, stage of diagnosis and theapproach used in treatment. Emerging studies on leukemia focuses onunderstanding genes and the development of leukemia vaccines. Otherstudies have focuses on chromosomal translocations as a way ofassessing how abnormalities in white blood cell development could becorrected.

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