Page 36 - IJSA, Vol. 4, No 2, 2021

International Journal of Science Annals, Vol. 5, No. 1-2, 2022
рrint ISSN: 2617-2682; online ISSN: 2707-3637; DOI:10.26697/ijsa

Discussion preference. Additionally, polychemotherapy is advised
CML is a disease that results from the reciprocal for these patients. Patients who have had TKI treatment
translation of genes on chromosomes 9 and 22 (Asif et before and go on to develop AP or BC are regarded as
al., 2016). The fused BCR-ABL protein has altered receiving TKI treatment that has not previously been
tyrosine kinase activity (Rajkumar et al., 2016). given. Allogenic stem cell transplantation is the best
The prognosis for CML patients depends on the disease treatment choice for CML-CP patients who have grown
stage at presentation, although even for people diagnosed resistant to at least two TKIs (Hegde et al., 2020).
in CP, survival rates might vary significantly. Patients After a BC diagnosis, the average survival time is thought
with chronic phase CML have myeloid cells at all stages to be 2-4 months. There are noticeable differences in the
of maturity (CP). Contrary to acute myeloid leukaemia proliferation, differentiation, adhesion, and apoptosis of
(AML), the flow cytometry (FC) approach enables the malignant cells during the blast crisis compared to those
detection of aberrant cell surface markers. FC is a during the chronic phase, which is well recognised. New,
straightforward diagnostic tool for (CP-CML) since it is non-random molecular or genetic alterations are thought
used to estimate the proportions of immature cells (Blast) to be the cause of the blast transformation. Trisomy 8,
in the late stages of the disease. This is a disease in adults trisomy 19, isochromosome 17, and mutations in the p53,
and extremely rare in childhood. This retrospective study RB, or RAS pathways are the reported most frequent
analyzed 43 cases of chronic myeloid leukemia – blast genetic anomalies. In myeloid BC, inactivating mutations
crisis over a period of 5 years. In the present study on of the genes p53 and RUNX1 are present, whereas
flowcytometric analysis, the most common blast inactivating mutations of the genes CDKN2A/B have
phenotype in the blast crisis was myeloid (62.7%) been found in lymphoid blast crisis. Response rates to
followed by B-lymphoid blast crisis (32.5%) and mixed normal induction therapy are less than 20–30% for CML-
phenotypic acute leukemia (4.7%). Out of two cases, of BC with an unique blast phenotype. Similar to other cases
MPAL, one case was of T-Myeloid and the other was of of CML with BC, patients with the erythroid or
B-Myeloid phenotypic blast crisis. A study conducted megakaryocytic blast phenotype get the same care. Cases
earlier also showed similar results (Narang et al., 2016). with lymphoblastic differentiation, on the other hand, are
Their study was comprised of 15 cases, which showed 14 managed as acute lymphoblastic leukaemia (Hegde et al.,
cases of myeloid blast crisis and a single case of 2020).
lymphoid (B-lineage) blast crisis. The evolution of CML It is suggested that molecular or genetic changes, such as
into blast crisis is common in myeloid type followed by trisomy 8, trisomy 19, isochromosome 17, t(3;21),
lymphoid type (Shi et al., 2015). A previous study also mutations in p53, RB gene, RAS pathway, or p16/ARF
showed blast crises in CML are of myeloid phenotype in pathway, are responsible for the blast transformation of
the majority of cases and lymphoid phenotype in 30% of CML. T-cell acute lymphoblastic leukaemia (T-ALL)
cases (Bonifacio et al., 2019). and BCR-ABL1-positive bilineage leukaemia might be
Chronic immunological dysfunction and T-cell fatigue difficult to distinguish from CML blast crisis of T-cell
are brought on by CML, a disease that primarily results lineage. De novo BCR-ABL1-positive T-cell ALL has
from long-term immune cell activation in an several characteristics, such as bone marrow
immunosuppressive milieu. involvement, small BCR breakpoint mutations, TCR
In the present study, we found four cases of B-lymphoid gene rearrangement mutations, children or teenage age
blast crisis with aberrant co-expression of CD13 and group, and no prior history of CML. Clonal T-cell gene
CD33 along with one case of myeloid blast crisis with rearrangement (TCR) is not usually present in early
aberrant expression of CD7. Another study conducted by immature T-cell neoplasms (like T-ALL), therefore its
Hegde et al. (2020) on chronic myeloid leukemia showed absence does not always rule out a T-cell blast
two cases displaying mixed phenotypic features catastrophe. A diagnosis of CML in a T-cell blast crisis
comprising each one of myeloid and megakaryocytic would be supported by BCR-ABL1 positive in both
differentiation. The treatment of CML-BP patients myeloid and lymphoid cells, as opposed to just the
depends on the immunophenotype of the blast population lymphoid component as it was found in our case.
hence it is mandatory to do flowcytometric analysis in 5–10% of CML patients eventually progress to advanced
each and every case of blast crisis (Assi & Short, 2020; phase while on therapy, despite the ground-breaking
Wang et al., 2021). Atypical lymphoblast populations in results TKI in CP-CML achieved. Most of the processes
CML are listed as a potential sign of an aggressive underlying TKI failure, the development of illness, and
disease course in the WHO classification of myeloid cytogenetic changes are yet unclear. TKI failure is caused
neoplasms (Arber et al., 2016; Chen et al., 2020). There by BCR-ABL1 dependent mechanisms, including
are some study limitations, including the fact that it was mutations in the ABL1 kinase domain, amplification of
conducted at just one hospital and there was no patient the BCR-ABL1 oncogene, and high levels of BCR-ABL1
follow-up. Newly diagnosed cases of CML-BC are mRNA expression. When the anaplastic threshold is
treated with first-generation TKIs, according to European achieved and additional oncogenes eventually cause
Leukemia Net (ELN) 2018 data (imatinib, nilotinib, progression in a BCR-ABL1-independent manner,
dasatinib and bosutinib). Third or fourth generation TKIs unchecked BCR-ABL1 signalling causes genomic
should be used to treat patients who do not react to first instability and a more chaotic state. The increased
generation TKIs. For patients with the BCR-ABL coding aggressive behaviour of CML clones expressing high
domain T315I mutation, ponatinib is the TKI of amounts of BCR-ABL1 can be explained by both

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