Co-occurrence of these disease entities is very rare and typically involves presence of common p190 or p210 BCR/ABL fusion transcript (responsible for CML) along with JAK2V617F mutation (most common driver mutation in Ph-negative MPNs).
We report two cases of pediatric patients with a diagnosis of CML who presented co-expression of the p210 and p190 transcripts during progression to the blastic phase.
In this study, we report the case of a Philadelphia (Ph) positive chronic myelogenous leukemia (CML) patient with the presence of p190 and p210 BCR-ABL1 mRNA fusion transcripts derived from e1a2 and b3a2 BCR-ABL1 genomic rearrangements, respectively.
We designed a novel multiplex in-cell reverse transcription-polymerase chain reaction method for the simultaneous detection and differentiation of p190 and p210 BCR-ABL mRNAs within single cells from the human chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia.
Four years later, the patient developed hematologic features of atypical CML with blood monocytosis, t(9;22) and much greater (100 fold) p190 BCR-ABL transcript levels.
These results do not support the hypothesis that P230 BCR/ABL induces a distinct and less aggressive form of CML in humans, and suggest that the rarity of P190 BCR/ABL in human CML may reflect infrequent BCR intron 1 breakpoints during the genesis of the Ph chromosome in stem cells, rather than intrinsic differences in myeloid leukemogenicity between P190 and P210.
We performed RT-PCR on samples from CML patients in chronic phase to determine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices.
We investigated this possibility by studying peripheral blood leukocytes from normal individuals and various hematopoietic cell lines for the presence and expression of the p210 and the p190 types of the BCR-ABL gene associated with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia.
Leukemic cells from patients with CML express the p210 form of the bcr-abl oncogene, whereas in adult Ph+ ALL approximately 50% of cases express the p190 form of the bcr-abl oncogene, and the other 50% express the same p210 gene as is found in CML.
This case differs from the previously reported cases of "p190" CML in that the patient presented without abnormal hematopoietic features other than those found in typical CML and provides further evidence that the p190 mRNA is not sufficient to cause an acute rather than chronic leukemia.
The median ratio of p190 to p210 BCR-ABL mRNA was not significantly different between chronic phase CML (1.9 x 10(-4)) and CML in blast crisis (1.7 x 10(-4)).
To investigate the hypothesis that the production of P190 may be associated with the progression from chronic phase to blast crisis in CML, we used polymerase chain reaction to analyze blood from 37 patients with accelerated phase/blast crisis CML for the transcripts coding for the P210BCR-ABL and P190BCR-ABL.
The shorter p190 protein is associated almost only with ALL and AML, while the protein p210 is present in both chronic phase and blast crisis of CML and also in 50% of Philadelphia-positive (Ph1+) ALL.
The lack of rearrangements within the M-bcr gene, together with demonstration in one case of the Ph' + AL specific p190 protein product, pointed against the occurrence of chronic myeloid leukemias presenting in blastic transformation.
Philadelphia chromosome positive acute lymphocytic leukemia and chronic myelogenous leukemia are strongly associated with two distinct forms of bcr-abl chimeric protein, known as P190 and P210, respectively.